1,968 results match your criteria European Journal of Drug Metabolism and Pharmacokinetics[Journal]


In Vitro Study of the Enzymatic and Nonenzymatic Conjugation of Treosulfan with Glutathione.

Eur J Drug Metab Pharmacokinet 2019 Apr 16. Epub 2019 Apr 16.

Department of Physical Pharmacy and Pharmacokinetics, Poznan University of Medical Sciences, 6 Święcickiego Street, 60-781, Poznań, Poland.

Background And Objectives: Treosulfan (dihydroxybusulfan), licensed for the treatment of ovarian carcinoma, is investigated in clinical trials as a myeloablative agent for conditioning prior to hematopoietic stem cell transplantation. Clinical experience shows that treosulfan exhibits lower organ toxicity than busulfan, including hepatotoxicity. Elimination of busulfan primarily via enzymatic conjugation with glutathione (GSH) in the liver is considered to be the main cause of the drug's hepatotoxicity and interpatient clearance variability. Read More

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http://link.springer.com/10.1007/s13318-019-00555-x
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http://dx.doi.org/10.1007/s13318-019-00555-xDOI Listing
April 2019
1 Read

Inhibitory Effect of Vonoprazan on the Metabolism of [C]Prasugrel in Human Liver Microsomes.

Eur J Drug Metab Pharmacokinet 2019 Apr 16. Epub 2019 Apr 16.

Global Drug Metabolism and Pharmacokinetics, Takeda Pharmaceuticals International Co., 35 Landsdowne Street, Cambridge, MA, 02139, USA.

Background And Objectives: A recent report indicated that the pharmacodynamic interaction between clopidogrel and vonoprazan leading to attenuation of the anti-platelet effect of clopidogrel was unlikely to be caused by the inhibition of cytochrome P450 (CYP) 2B6, CYP2C19, or CYP3A4/5 by vonoprazan, based on in vitro CYP inhibition data. The current report investigates another important antiplatelet inhibitor, prasugrel, that is also activated through metabolism by CYP2B6, CYP2C19 and CYP3A4/5, for its CYP-based DDI potential with vonoprazan. The report describes in vitro metabolic inhibition assessments using radiolabeled prasugrel and human liver microsomes (HLMs). Read More

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http://dx.doi.org/10.1007/s13318-019-00554-yDOI Listing

Clinical and Pharmacokinetic Outcomes of Peak-Trough-Based Versus Trough-Based Vancomycin Therapeutic Drug Monitoring Approaches: A Pragmatic Randomized Controlled Trial.

Eur J Drug Metab Pharmacokinet 2019 Mar 27. Epub 2019 Mar 27.

Clinical Pharmacy and Practice Section, College of Pharmacy, Qatar University, P.O. Box 2713, Doha, Qatar.

Background: Vancomycin therapeutic drug monitoring (TDM) is based on achieving 24-h area under the concentration-time curve to minimum inhibitory concentration cure breakpoints (AUC/MIC). Approaches to vancomycin TDM vary, with no head-to-head randomized controlled trial (RCT) comparisons to date.

Objectives: We aimed to compare clinical and pharmacokinetic outcomes between peak-trough-based and trough-only-based vancomycin TDM approaches and to determine the relationship between vancomycin AUC/MIC and cure rates. Read More

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http://link.springer.com/10.1007/s13318-019-00551-1
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http://dx.doi.org/10.1007/s13318-019-00551-1DOI Listing
March 2019
7 Reads

Comparative Evaluation of Median Versus Youden Index Dichotomization Methods: Exposure-Response Analysis of Mycophenolic Acid and Acyl-Glucuronide Metabolite.

Eur J Drug Metab Pharmacokinet 2019 Mar 16. Epub 2019 Mar 16.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.

Background And Objectives: Dichotomization of pharmacokinetic exposure measures in exposure-response relationship studies provides results that are interpretable in clinical care. Several methods exist in the literature on how to define the cut-off values needed for the dichotomization process. Commonly, the sample median is utilized to define the dichotomizing value; however, statistical methods based on the exposure metric and its association with the outcome are argued to result in a more proper definition of the optimal cut-point. Read More

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http://dx.doi.org/10.1007/s13318-019-00550-2DOI Listing
March 2019
2 Reads

Inhibitory Mechanisms of Myricetin on Human and Rat Liver Cytochrome P450 Enzymes.

Eur J Drug Metab Pharmacokinet 2019 Mar 1. Epub 2019 Mar 1.

First Affiliated Hospital of Jiaxing University, Jiaxing, China.

Background And Objectives: Myricetin is a flavonoid compound that is abundant in teas, red wine, berries, herbs and vegetables with a variety of pharmacological properties such as antioxidant, anti-inflammatory and anti-cancer effects. Although there are in vitro studies showing that myricetin inhibits human cytochrome P450 (CYP) 2D6 and CYP3A, the inhibitory mechanisms of myricetin on CYP enzymes are still unclear. The aim of this study was to evaluate the inhibitory effects of myricetin on human and rat CYPs, including CYP3A2/3A4, CYP2B1/2B6, CYP2C9/2C11 and CYP2D1/2D6. Read More

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http://link.springer.com/10.1007/s13318-019-00546-y
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http://dx.doi.org/10.1007/s13318-019-00546-yDOI Listing
March 2019
8 Reads

Pharmacokinetics of the Novel Nonsteroidal Mineralocorticoid Receptor Antagonist Finerenone (BAY 94-8862) in Individuals with Mild or Moderate Hepatic Impairment.

Eur J Drug Metab Pharmacokinet 2019 Mar 1. Epub 2019 Mar 1.

CRS Clinical Research Services Kiel GmbH, Kiel, Germany.

Background And Objectives: Finerenone (BAY 94-8862) is a selective, nonsteroidal mineralocorticoid receptor antagonist. The aim of this study was to assess the effect of mild or moderate hepatic impairment on the pharmacokinetics, safety and tolerability of finerenone.

Methods: The study was conducted in a single-center, nonrandomized, noncontrolled, nonblinded observational design with group stratification. Read More

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http://dx.doi.org/10.1007/s13318-019-00547-xDOI Listing
March 2019
1 Read

Glucuronidation of D-Luciferin In Vitro: Isoform Selectivity and Kinetics Characterization.

Eur J Drug Metab Pharmacokinet 2019 Feb 28. Epub 2019 Feb 28.

School of Life Science and Medicine, Dalian University of Technology, Panjin, China.

Background: D-luciferin is one of the most commonly used substrates in bioluminescence imaging for real-time monitoring of sophisticated biological processes in models of human biology or disease in vitro and in vivo. D-luciferin is rapidly cleared from blood circulation after being exogenously delivered in vivo and the presence of phenolic groups indicates that glucuronide conjugation is a possible metabolic pathway for the compound.

Objectives: This study aimed to characterize the glucuronidation pathway of D-luciferin in human liver microsomes (HLM) and human intestine microsomes (HIM). Read More

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http://dx.doi.org/10.1007/s13318-019-00549-9DOI Listing
February 2019
1 Read

Fluctuations in Pharmacokinetics Profiles of Monoclonal Antibodies.

Eur J Drug Metab Pharmacokinet 2019 Feb 27. Epub 2019 Feb 27.

Laboratory of Reproductive Immunology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.

Monoclonal antibodies (mAbs) are a group of drugs with predicted slow linear and target-mediated distribution and elimination. Visual inspection of published pharmacokinetic profiles of mAbs frequently reveals plateaus in the distribution phase or an increasing concentration many days after a single intravenous dose. A question which has been left unanswered until now is whether mAbs undergo recirculation mechanisms. Read More

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http://dx.doi.org/10.1007/s13318-019-00548-wDOI Listing
February 2019
2 Reads

Influence of Obesity and Type 2 Diabetes Mellitus on the Pharmacokinetics of Tramadol After Single Oral Dose Administration.

Eur J Drug Metab Pharmacokinet 2019 Feb 18. Epub 2019 Feb 18.

Department of Clinical Pharmacy and Biopharmacy, Poznań University of Medical Sciences, ul. Św. Marii Magdaleny 14, 61-861, Poznań, Poland.

Background And Objectives: The number of overweight, obese and diabetic patients is constantly increasing. Metabolic disorders may affect the pharmacokinetics of drugs, e.g. Read More

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http://dx.doi.org/10.1007/s13318-019-00543-1DOI Listing
February 2019
2 Reads

Enhancing Curcumin Oral Bioavailability Through Nanoformulations.

Eur J Drug Metab Pharmacokinet 2019 Feb 15. Epub 2019 Feb 15.

Institute of Chemical Technology, Mumbai, India.

Curcumin is a promising therapeutic agent that exhibits manifold therapeutic activities. However, it is challenging to study curcumin as it exhibits poor aqueous solubility and low permeability and it is a substrate for P-glycoprotein (P-gp). It is readily metabolized in the body, but many active metabolites of curcumin have been identified that could also be exploited for therapy. Read More

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http://dx.doi.org/10.1007/s13318-019-00545-zDOI Listing
February 2019
3 Reads

Tacrolimus Variability: A Cause of Donor-Specific Anti-HLA Antibody Formation in Children.

Eur J Drug Metab Pharmacokinet 2019 Feb 8. Epub 2019 Feb 8.

Department of Pediatric Nephrology, School of Medicine, Akdeniz University, 07059, Antalya, Turkey.

Background And Objectives: The most important determinant of long-term graft survival in renal transplantation is adequate immunosuppression. Inadequate immunosuppression may lead to graft loss due to the presence of anti-HLA antibody. The aim of this study was to investigate the effect of variability in tacrolimus blood concentration on anti-HLA antibody development in pediatric recipients of living-donor renal transplants. Read More

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http://dx.doi.org/10.1007/s13318-019-00544-0DOI Listing
February 2019
1 Read

Effect of Gender on the Pharmacokinetics of ON 123300, A Dual Inhibitor of ARK5 and CDK4/6 for the Treatment of Cancer, in Rats.

Eur J Drug Metab Pharmacokinet 2019 Jan 30. Epub 2019 Jan 30.

Onconova Therapeutics, Inc., Newtown, PA, USA.

Background And Objectives: ON 123300, a small molecule dual inhibitor of the c-MYC activated kinases ARK5 and CDK4/6, is being developed as a novel drug candidate for the treatment of cancer. The objective of this research was to evaluate gender differences in the in vitro metabolism and in vivo systemic exposure of ON 123300 in rats.

Methods: In vitro metabolism experiments (n = 2/group) were performed in rat liver microsomes from male and female donors. Read More

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http://dx.doi.org/10.1007/s13318-019-00542-2DOI Listing
January 2019

In-Vivo Degradation of DNA-Based Therapeutic BC 007 in Humans.

Eur J Drug Metab Pharmacokinet 2019 Jan 23. Epub 2019 Jan 23.

Department of Chemistry, NMR Facility, Humboldt University of Berlin, Brook-Taylor-Straße 2, 12489, Berlin, Germany.

Background And Objectives: Since there is no clear evidence in the literature to show how non-modified single-stranded DNA (ssDNA) drugs are metabolized in humans, we assessed the metabolism of BC 007, an ssDNA therapeutic, under development as a neutralizer of autoantibodies against G-protein-coupled receptors. In-vitro, investigating its stability in monkey plasma and serum, a successive 3'-exonuclease degradation resulting in several n-x degradation products has been previously reported. Here, we investigated the metabolism of BC 007 in humans after intravenous application to autoantibody-positive healthy subjects, in line with Phase I safety testing. Read More

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http://dx.doi.org/10.1007/s13318-019-00541-3DOI Listing
January 2019

Correction to: Effects of Phenothiazines on Aldehyde Oxidase Activity Towards Aldehydes and N-Heterocycles: an In Vitro and In Silico Study.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):287

School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Unfortunately, the original article was published with error in author names. The author names are corrected here by this correction paper. The original article has been corrected. Read More

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http://dx.doi.org/10.1007/s13318-018-00539-3DOI Listing
April 2019
1 Read

Clinical Pharmacokinetics of a Lipid-Based Formulation of Risperidone, VAL401: Analysis of a Single Dose in an Open-Label Trial of Late-Stage Cancer Patients.

Eur J Drug Metab Pharmacokinet 2019 Jan 9. Epub 2019 Jan 9.

Ariana Pharmaceuticals, 43-47 Av de la Grande Armée, 75116, Paris, France.

Background And Objectives: A clinical trial was conducted to measure and analyse the pharmacokinetic parameters of a lipid formulation of risperidone, VAL401. The VAL401 formulation is designed to repurpose risperidone from an antipsychotic to an adenocarcinoma treatment, with the lipid formulation altering the cellular uptake of risperidone, thus enabling anticancer biology to be exhibited in preclinical testing.

Methods: This first human trial of VAL401 measured the concentrations of risperidone and its primary metabolite, 9-hydroxyrisperidone, in the blood of patients after treatment with a single 2-mg dose of VAL401. Read More

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http://dx.doi.org/10.1007/s13318-018-00538-4DOI Listing
January 2019
2 Reads

Population Pharmacokinetic Modelling of Pyrazinamide and Pyrazinoic Acid in Patients with Multi-Drug Resistant Tuberculosis.

Eur J Drug Metab Pharmacokinet 2019 Jan 8. Epub 2019 Jan 8.

School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville, 7535, Cape Town, South Africa.

Background And Objectives: Pyrazinamide, a drug used in the regimen for the treatment of drug-sensitive tuberculosis, is also used for the treatment of multidrug-resistant tuberculosis (MDR-TB). We aimed to describe the population pharmacokinetics of pyrazinamide and its major metabolite, pyrazinoic acid, in patients with MDR-TB and characterise the effects of demographic variables.

Methods: This was a non-randomised clinical study involving 51 adult patients admitted for the intensive phase of MDR-TB treatment. Read More

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http://dx.doi.org/10.1007/s13318-018-00540-wDOI Listing
January 2019
2 Reads

Population Pharmacokinetics and Exposure-Response of Lithium Carbonate in Patients Based on Tubular Reabsorption Mechanisms.

Eur J Drug Metab Pharmacokinet 2018 Dec 7. Epub 2018 Dec 7.

Department of Pharmacy, Fukuoka University Hospital, 7-45-1 Nanakuma, Zyounan-ku, Fukuoka, 814-0180, Japan.

Background And Objective: Lithium, which is used to treat bipolar disorder, has a narrow therapeutic blood concentration range and quickly reaches clinically toxic levels. We performed a population pharmacokinetic analysis with a lithium tubular reabsorption model including urinary pH and investigated the relationship between blood lithium concentration and tremor as a side effect.

Methods: Routine clinical data, including 389 serum concentrations, were collected from 214 patients orally administered an adjusted amount of lithium carbonate. Read More

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http://dx.doi.org/10.1007/s13318-018-0536-0DOI Listing
December 2018
2 Reads

Advanced In Vitro HepaRG Culture Systems for Xenobiotic Metabolism and Toxicity Characterization.

Eur J Drug Metab Pharmacokinet 2018 Dec 10. Epub 2018 Dec 10.

Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group Centre for Pharmacy and Health Research, Room 3-142D, 11361-87 Ave, Edmonton, AB, T6G 2E1, Canada.

Several HepaRG three-dimensional (3D) in vitro model systems have been developed to improve the predictability of xenobiotic metabolism and toxicity. In this review, we present a detailed summary and critique of the performance of various HepaRG 3D models compared to the conventional 2D monolayer culture. HepaRG 3D models can be broadly categorized into (1) scaffold-free, (2) scaffold-based, and (3) bioartificial liver (BAL) models. Read More

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http://dx.doi.org/10.1007/s13318-018-0533-3DOI Listing
December 2018
20 Reads

Population Pharmacokinetics, Safety and Tolerability of Extended-Release Bupropion and Its Three Metabolites in Chinese Healthy Volunteers.

Eur J Drug Metab Pharmacokinet 2018 Dec 5. Epub 2018 Dec 5.

Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, 4/F, 604 Lingling Road, Shanghai, 200030, China.

Background And Objective: Bupropion is used for the treatment of major depressive disorder. We determined the pharmacokinetics, safety, and tolerability of extended-release bupropion XL in healthy Chinese volunteers.

Methods: This open-label, single-center pharmacokinetic study was conducted between May 2016 and June 2016. Read More

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http://dx.doi.org/10.1007/s13318-018-0537-zDOI Listing
December 2018
12 Reads
1.312 Impact Factor

Development of a Population Pharmacokinetic Model of Vancomycin and its Application in Chinese Geriatric Patients with Pulmonary Infections.

Eur J Drug Metab Pharmacokinet 2018 Nov 30. Epub 2018 Nov 30.

Department of Nephrology, Peking University First Hospital, No.1 Dahongluochang Street, Xicheng District, Beijing, China.

Background: The optimal use of vancomycin in the elderly requires information about the drug's pharmacokinetics and the influence of various factors on the drug's disposition. However, because of sampling restrictions, it is often difficult to perform traditional pharmacokinetic studies in elderly patients.

Objective: This study was conducted to estimate the population pharmacokinetics of vancomycin in Chinese geriatric patients (age ≥ 65 years) with pulmonary infections and to explore the clinical application of this information for vancomycin dose individualization. Read More

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http://dx.doi.org/10.1007/s13318-018-0534-2DOI Listing
November 2018
3 Reads
1.312 Impact Factor

Comparison of the Pharmacokinetic Profiles of Ceftriaxone Used Alone and Combined with Danhong Injection in Old Rats.

Eur J Drug Metab Pharmacokinet 2018 Dec 3. Epub 2018 Dec 3.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources, Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, No. 138, Xianlin Avenue, Nanjing, 210046, People's Republic of China.

Background And Objectives: Danhong injection is the most commonly prescribed adjuvant drug applied for the treatment of cardiovascular and cerebrovascular diseases in China. Ceftriaxone is usually prescribed along with Danhong injection to elderly patients with complications. However, the pharmacokinetic interactions between these two medications have not been investigated. Read More

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http://dx.doi.org/10.1007/s13318-018-0530-6DOI Listing
December 2018
1 Read

A Gallbladder-Based Enterohepatic Circulation Model for Pharmacokinetic Studies.

Eur J Drug Metab Pharmacokinet 2018 Nov 28. Epub 2018 Nov 28.

Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, Minneapolis, MN, USA.

Background And Objectives: Strategies for modeling the enterohepatic circulation (EHC) process reported in the literature vary; however, gallbladder-based models currently provide the best physiological representation of the process. Regardless, the addition of a gallbladder to the model does not fully depict the physiology of EHC. A more physiological gallbladder-based EHC model is needed. Read More

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http://link.springer.com/10.1007/s13318-018-0535-1
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http://dx.doi.org/10.1007/s13318-018-0535-1DOI Listing
November 2018
26 Reads

Conversion from Twice-Daily Prograf to Once-Daily Advagraf in Multi-ethnic Asian Adult Renal Transplant Recipients With or Without Concomitant Use of Diltiazem: Impact of CYP3A5 and MDR1 Genetic Polymorphisms on Tacrolimus Exposure.

Eur J Drug Metab Pharmacokinet 2018 Nov 23. Epub 2018 Nov 23.

National University Centre for Organ Transplantation, National University Hospital, Singapore, Republic of Singapore.

Background And Objectives: Tacrolimus is the mainstay of immunosuppression in renal transplantation. Given that once-daily administration improves patient compliance, 1:1 dose conversion from twice-daily Prograf to once-daily Advagraf is recommended. Although cytochrome P450 (CYP) 3A5 and multi-drug resistance 1 (MDR1) polymorphisms influence tacrolimus concentrations, it is unknown if these impact on conversion. Read More

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http://dx.doi.org/10.1007/s13318-018-0531-5DOI Listing
November 2018
11 Reads

A Physiologically Based Pharmacokinetic Model for Optimally Profiling Lamotrigine Disposition and Drug-Drug Interactions.

Eur J Drug Metab Pharmacokinet 2018 Nov 20. Epub 2018 Nov 20.

School of Pharmacy, Husson University, 1 College Circle, Bangor, ME, 04401, USA.

Background And Objectives: Lamotrigine (Lamictal) is a broad-spectrum antiepileptic drug available in both immediate-(IR) and extended-release (XR) formulations. Here, we present a new physiologically based pharmacokinetic (PBPK) model for IR and XR formulations of lamotrigine to predict disposition in adults and children, plus drug-drug interactions (DDIs).

Methods: Models for lamotrigine IR and XR formulations were constructed using a Simcyp Simulator. Read More

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http://dx.doi.org/10.1007/s13318-018-0532-4DOI Listing
November 2018
13 Reads

Retraction Note to: Changes of Absorptive and Secretory Transporting System of (1 → 3) β-D-glucan Based on Efflux Transporter in Indomethacin-induced Rat.

Eur J Drug Metab Pharmacokinet 2018 Dec;43(6):769

Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.

The Editor-in-Chief has retracted this article [1] based on an investigation by the Ministry of Education, Culture, Sports, Science and Technology, Japan, which found that the article contained overlap with a previously published article by Kalitsky-Szirtes J, et al. [2]. Read More

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http://dx.doi.org/10.1007/s13318-018-0529-zDOI Listing
December 2018
1 Read

Clinical Application of Pharmacokinetics: Basis for Rational Dose Selection in a Critically Ill Patient on Renal Replacement Therapy.

Eur J Drug Metab Pharmacokinet 2018 Nov 13. Epub 2018 Nov 13.

Pharmacology and Toxicology Department, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića Street, 69, 34000, Kragujevac, Serbia.

Background: Individualizing drug dosing regimens in critically ill patients on renal replacement therapy is a challenge to clinicians as guidelines are often imprecise and specific-validated pharmacokinetic software is unavailable.

Objective: A case of a septic patient on hemodialysis is presented, where a quick solution for antibiotic dose adjustment based on the application of pharmacokinetic principles was found.

Methods: The dose adjustment was made in two steps-the first step was to calculate total antibiotic clearance (using the formula: total drug clearance = dialysate flow rate × fraction of unbound drug in plasma + extrarenal clearance), and the second step was to calculate maintenance dose based on target plasma concentrations in steady-state (using the formula: maintenance dose = target plasma concentration × total drug clearance × dose interval). Read More

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http://link.springer.com/10.1007/s13318-018-0524-4
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http://dx.doi.org/10.1007/s13318-018-0524-4DOI Listing
November 2018
11 Reads

Hepatic Cytochrome P450 Activity and Nitric Oxide Production During Multiple Ovalbumin Challenges.

Eur J Drug Metab Pharmacokinet 2018 Nov 8. Epub 2018 Nov 8.

Laboratory of Pharmaceutics, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Bouji Nishihama, Yamashiro-cho, Tokushima, Tokushima, 770-8514, Japan.

Background And Objectives: Mast cell-mediated allergic diseases are a significant global health problem. Nitric oxide (NO) produced by acute type 1 allergies greatly suppresses hepatic cytochrome P450 (CYP) metabolism. A recent in vitro study demonstrated that repeated FcεRI-mediated activation intrinsically modulates mast cell function. Read More

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http://link.springer.com/10.1007/s13318-018-0527-1
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http://dx.doi.org/10.1007/s13318-018-0527-1DOI Listing
November 2018
16 Reads

Pharmacokinetics and Pharmacodynamics of Cabotegravir, a Long-Acting HIV Integrase Strand Transfer Inhibitor.

Eur J Drug Metab Pharmacokinet 2018 Nov 1. Epub 2018 Nov 1.

Gestione Ambulatoriale Politerapie (GAP) Outpatient Clinic, ASST Fatebenefratelli Sacco University Hospital, via GB Grassi 74, 20157, Milan, Italy.

Available antiretroviral drugs have demonstrated effectiveness in both pre-exposure prophylaxis and treatment of HIV infection. However, some concerns still persist regarding these therapies, mainly related to patient adherence, drug toxicity and dosing convenience. Cabotegravir is a potent integrase strand transfer inhibitor with a chemical structure similar to dolutegravir that is under clinical evaluation both as oral and long-acting injectable (LAI) formulations for both the prevention or treatment of HIV infection. Read More

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http://dx.doi.org/10.1007/s13318-018-0526-2DOI Listing
November 2018
2 Reads

Pharmacokinetics and Safety of Recombinant Human Interleukin-1 Receptor Antagonist GR007 in Healthy Chinese Subjects.

Eur J Drug Metab Pharmacokinet 2018 Oct 31. Epub 2018 Oct 31.

Department of Pharmacy, Peking University First Hospital, Beijing, 100034, China.

Background And Objectives: The recombinant human interleukin-1 receptor antagonist (rhIL-1Ra) GR007 is a candidate drug with the potential to prevent the toxicity induced by chemotherapy agents by blocking the IL-1 signaling pathway. The aim of this study was to assess the pharmacokinetics and safety of GR007 in healthy Chinese subjects.

Methods: Thirty subjects received a single intramuscular injection of 30 mg (n = 10), 90 mg (n = 10), or 150 mg (n = 10) GR007. Read More

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http://link.springer.com/10.1007/s13318-018-0523-5
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http://dx.doi.org/10.1007/s13318-018-0523-5DOI Listing
October 2018
8 Reads

Effects of Phenothiazines on Aldehyde Oxidase Activity Towards Aldehydes and N-Heterocycles: an In Vitro and In Silico Study.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):275-286

School of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.

Background: Aldehyde oxidase (AOX) is an important molybdenum-containing enzyme with high similarity with xanthine oxidase (XO). AOX involved in the metabolism of a large array of aldehydes and N-heterocyclic compounds and its activity is highly substrate-dependent.

Objectives: The aim of this work was to study the effect of five important phenothiazine drugs on AOX activity using benzaldehyde and phenanthridine as aldehyde and N-heterocyclic substrates, respectively. Read More

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http://dx.doi.org/10.1007/s13318-018-0514-6DOI Listing
April 2019
1 Read

Population Pharmacokinetic Analysis of Immediate-Release Oral Tacrolimus Co-administered with Mycophenolate Mofetil in Corticosteroid-Free Adult Kidney Transplant Recipients.

Eur J Drug Metab Pharmacokinet 2018 Oct 30. Epub 2018 Oct 30.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.

Background And Objective: Tacrolimus is the mainstay calcineurin inhibitor frequently administered with mycophenolic acid with or without corticosteroids to prevent graft rejection in adult kidney transplant recipients. The primary objective of this study was to develop and evaluate a population pharmacokinetic model characterizing immediate-release oral tacrolimus co-administered with mycophenolate mofetil (a pro-drug of mycophenolic acid) in adult kidney transplant recipients on corticosteroid-free regimens. The secondary objective was to investigate the effects of clinical covariates on the pharmacokinetics of tacrolimus, emphasizing the interacting effects of mycophenolic acid. Read More

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http://dx.doi.org/10.1007/s13318-018-0525-3DOI Listing
October 2018
4 Reads

In Vitro Assessment of Potential for CYP-Inhibition-Based Drug-Drug Interaction Between Vonoprazan and Clopidogrel.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):217-227

d3 Medicine, A Certara Company, London, UK.

Background And Objectives: It was recently proposed that CYP-mediated drug-drug interactions (DDIs) of vonoprazan with clopidogrel and prasugrel can attenuate the antiplatelet actions of the latter two drugs. Clopidogrel is metabolized to the pharmacologically active metabolite H4 and its isomers by multiple CYPs, including CYP2C19 and CYP3A4. Therefore, to investigate the possibility of CYP-based DDIs, in vitro metabolic inhibition studies using CYP probe substrates or radiolabeled clopidogrel and human liver microsomes (HLMs) were conducted in this work. Read More

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http://link.springer.com/10.1007/s13318-018-0521-7
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http://dx.doi.org/10.1007/s13318-018-0521-7DOI Listing
April 2019
5 Reads

Population Pharmacokinetic Modeling of Azithromycin Eyedrops in Tears Following Single-Dose Topical Administration in Healthy Volunteers.

Eur J Drug Metab Pharmacokinet 2018 Oct 24. Epub 2018 Oct 24.

Department of Pharmacy, Peking University First Hospital, Beijing, China.

Background And Objectives: The disposition of azithromycin in the human eye following topical administration has not been fully explored. Population pharmacokinetic (PopPK) modeling can allow useful conclusions to be drawn based on limited tear sampling data. The aim of this study was therefore to develop and evaluate a PopPK model of azithromycin eyedrops in tears, investigate typical model parameters, and identify potential covariates following single-dose ocular instillation. Read More

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http://link.springer.com/10.1007/s13318-018-0522-6
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http://dx.doi.org/10.1007/s13318-018-0522-6DOI Listing
October 2018
9 Reads

Mechanistic Assessment of the Effect of Omeprazole on the In Vivo Pharmacokinetics of Itraconazole in Healthy Volunteers.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):201-215

Australian Centre for Pharmacometrics and Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia.

Background And Objective: SUBA-itraconazole and Sporanox are two oral formulations of itraconazole. Drug-drug interactions with omeprazole have been previously reported; however, mechanistic understanding of the pharmacological and physiological interactions of omeprazole with orally administered itraconazole within a population modeling paradigm is lacking. The objective of this analysis was to mechanistically describe and quantify the effect of omeprazole on the pharmacokinetics of itraconazole and its major metabolite, hydroxyitraconazole from the SUBA itraconazole and Sporanox formulations. Read More

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http://dx.doi.org/10.1007/s13318-018-0519-1DOI Listing
April 2019
1 Read

Improved Oral Absorption of Quercetin from Quercetin Phytosome®, a New Delivery System Based on Food Grade Lecithin.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):169-177

Research and Development Department, Indena SpA, 20139, Milan, Italy.

Background And Objectives: The importance of quercetin and flavonoids in the diet and as food supplements is well known, and literature studies support their potential use to treat several human diseases. Many beneficial properties have been described for quercetin, so much effort has been directed into overcoming the major drawbacks of this natural compound-its poor solubility and low oral absorption. The aims of this study were to compare a new food-grade lecithin-based formulation of quercetin, Quercetin Phytosome, to unformulated quercetin in terms of solubility in simulated gastrointestinal fluids and oral absorption in a randomized crossover pharmacokinetic study of healthy volunteers. Read More

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http://link.springer.com/10.1007/s13318-018-0517-3
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http://dx.doi.org/10.1007/s13318-018-0517-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418071PMC
April 2019
16 Reads

Clinical Pharmacokinetics and Pharmacodynamics of Delafloxacin.

Eur J Drug Metab Pharmacokinet 2018 Oct 15. Epub 2018 Oct 15.

Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Room 3-142D, 11,361-87 Ave, Edmonton, AB, T6G 2E1, Canada.

Delafloxacin has recently received approval by the US Food and Drug Administration for the treatment of acute bacterial skin and skin structure infections. This article provides a balanced and comprehensive systematic critique of the literature in order to provide an up-to-date summary of its clinical pharmacology. Oral delafloxacin is rapidly absorbed and exhibits comparable exposure characteristics (300 mg intravenous versus 450 mg oral) between the two formulations, allowing easy transition from intravenous to oral therapy. Read More

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http://link.springer.com/10.1007/s13318-018-0520-8
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http://dx.doi.org/10.1007/s13318-018-0520-8DOI Listing
October 2018
18 Reads

Pharmacokinetics Comparison, Intestinal Absorption and Acute Toxicity Assessment of a Novel Water-Soluble Astragaloside IV Derivative (Astragalosidic Acid, LS-102).

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):251-259

Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, China.

Background And Objectives: Astragaloside IV (AGS IV) is the most important bioactive constituent of Radix Astragali. However, its disappointing clinical application is mainly caused by its very low solubility in biologic fluids, resulting in poor bioavailability after oral administration. We recently obtained a novel water-soluble derivative of AGS IV (astragalosidic acid, LS-102) that displayed significant cardioprotective potential against hypoxia-induced injury. Read More

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http://dx.doi.org/10.1007/s13318-018-0515-5DOI Listing
April 2019
2 Reads

Effect of 95% Ethanol Khat Extract and Cathinone on in vitro Human Recombinant Cytochrome P450 (CYP) 2C9, CYP2D6, and CYP3A4 Activity.

Eur J Drug Metab Pharmacokinet 2018 Oct 10. Epub 2018 Oct 10.

Department of Biomedical Science, The University of Nottingham Malaysia Campus, Jalan Broga, 43500, Semenyih, Selangor Darul Ehsan, Malaysia.

Background And Objective: A significant number of people worldwide consume khat on daily basis. Long term of khat chewing has shown negative impact on several organ systems. It is likely that these people are co-administered khat preparations and conventional medication, which may lead to khat-drug interactions. Read More

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http://dx.doi.org/10.1007/s13318-018-0518-2DOI Listing
October 2018
1 Read

Comparison of In Vitro Stereoselective Metabolism of Bupropion in Human, Monkey, Rat, and Mouse Liver Microsomes.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):261-274

Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Avenue, Pittsburgh, PA, 15282, USA.

Background And Objectives: Bupropion is an atypical antidepressant and smoking cessation aid associated with wide intersubject variability. This study compared the formation kinetics of three phase I metabolites (hydroxybupropion, threohydrobupropion, and erythrohydrobupropion) in human, marmoset, rat, and mouse liver microsomes. The objective was to establish suitability and limitations  for subsequent use of nonclinical species to model bupropion central nervous system (CNS) disposition in humans. Read More

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http://link.springer.com/10.1007/s13318-018-0516-4
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http://dx.doi.org/10.1007/s13318-018-0516-4DOI Listing
April 2019
11 Reads
1.312 Impact Factor

Clinical Pharmacokinetics of Second-Generation Triazoles for the Treatment of Invasive Aspergillosis and Candidiasis.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):139-157

Faculty of Medical Sciences, University of Kragujevac, Zmaj Jovina Street, 30, Kragujevac, 34000, Serbia.

Second-generation triazoles were developed in response to the quest for more efficacious and safer therapeutic options for the treatment of severe systemic aspergillosis and candidiasis. These agents include voriconazole, posaconazole, isavuconazole, and ravuconazole. The aim of this review was to present and compare the pharmacokinetic characteristics of second-generation triazoles for the treatment of invasive aspergillosis and candidiasis, emphasizing their clinical implications. Read More

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http://link.springer.com/10.1007/s13318-018-0513-7
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http://dx.doi.org/10.1007/s13318-018-0513-7DOI Listing
April 2019
17 Reads

Longitudinal Pharmacokinetics of Mycophenolic Acid in Elderly Renal Transplant Recipients Compared to a Younger Control Group: Data from the nEverOld Trial.

Eur J Drug Metab Pharmacokinet 2019 04;44(2):189-199

Renal Transplantation Service, Division of Urology, Hospital das Clínicas, São Paulo University School of Medicine, Av. Dr.Enéas de Carvalho Aguiar, 255, São Paulo, 05403-900, Brazil.

Background And Objectives: Elderly patients are increasingly likely to be recipients of transplants. However, the pharmacokinetics of mycophenolic acid (MPA) in this population are yet to be studied in detail. The objective of this study was to assess whether there were differences in MPA pharmacokinetic parameter values between elderly recipients and younger-adult recipients during the 6 months immediately following renal transplantation. Read More

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http://dx.doi.org/10.1007/s13318-018-0506-6DOI Listing
April 2019
5 Reads

Determination of the Pharmacokinetics and Tissue Distribution of Methyl 3,4-Dihydroxybenzoate (MDHB) in Mice Using Liquid Chromatography-Tandem Mass Spectrometry.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):237-249

Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.

Background And Objectives: Methyl 3,4-dihydroxybenzoate (MDHB) has the potential to prevent neurodegenerative diseases (NDDs). The present work aims to reveal the pharmacokinetics and tissue distribution characteristics of MDHB.

Methods: The pharmacokinetics and tissue distribution of MDHB were analyzed using LC-MS/MS after a single intragastric administration (50 to 450 mg/kg) in mice, and samples were collected from five animals at specific time points. Read More

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http://dx.doi.org/10.1007/s13318-018-0512-8DOI Listing
April 2019
3 Reads
1.312 Impact Factor

Pharmacokinetics and Bioavailability Enhancement of Baicalin: A Review.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):159-168

Department of Pharmacy, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Baicalin is one of the major bioactive components of Scutellaria radix, a Chinese herb that has been used since ancient times. Baicalin has various pharmacological activities, including antitumor, antimicrobial, and antioxidant, and has wide clinical applications. Baicalin displays a distinct pharmacokinetic profile including gastrointestinal hydrolysis, enterohepatic recycling, carrier-mediated transport, and complicated metabolism. Read More

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http://dx.doi.org/10.1007/s13318-018-0509-3DOI Listing
April 2019
22 Reads

Intestinal Absorption of Isoalantolactone and Alantolactone, Two Sesquiterpene Lactones from Radix Inulae, Using Caco-2 Cells.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):295-303

School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Road, Minhang District, Shanghai, 200240, People's Republic of China.

Background: Isoalantolactone and alantolactone are the main sesquiterpene lactones in Radix Inulae (dried root of Inula helenium L. or I. racemosa Hook. Read More

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http://link.springer.com/10.1007/s13318-018-0510-x
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http://dx.doi.org/10.1007/s13318-018-0510-xDOI Listing
April 2019
19 Reads

Correction to: Evaluation of Generic Methods to Predict Human Pharmacokinetics Using Physiologically Based Pharmacokinetic Model for Early Drug Discovery of Tyrosine Kinase Inhibitors.

Eur J Drug Metab Pharmacokinet 2019 Feb;44(1):133

Shanghai PharmoGo Co., Ltd, 3F, Block B, Weitai Building, No. 58, Lane 91, Shanghai, 200127, People's Republic of China.

The original version of this article unfortunately contained a mistake. Conflict of interest statement was incorrect. The corrected COI statement is given below. Read More

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http://dx.doi.org/10.1007/s13318-018-0511-9DOI Listing
February 2019
1 Read

The Influence of Diabetes Mellitus on Glucuronidation and Sulphation of Paracetamol in Patients with Febrile Neutropenia.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):289-294

Department of Clinical Pharmacy and Biopharmacy, Medical University of Poznań, Marii Magdaleny 14, 61-861, Poznań, Poland.

Background And Objectives: Numerous studies have confirmed the influence of diabetes mellitus on the pharmacokinetics of drugs. Paracetamol (APAP) is an antipyretic that is commonly used in febrile neutropenia (FN) therapy. APAP is chiefly metabolised by glucuronidation and sulphation. Read More

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http://dx.doi.org/10.1007/s13318-018-0508-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418056PMC
April 2019
5 Reads

Impact of Efavirenz Metabolism on Loss to Care in Older HIV+ Africans.

Eur J Drug Metab Pharmacokinet 2019 Apr;44(2):179-187

Department of Medicine, Perelman School of Medicine, University of Pennsylvania, 3910 Powelton Ave., 2nd Floor, Philadelphia, PA, 19104, USA.

BACKGROUND AND OBJECTIVE: Efavirenz is commonly used in Africa and is frequently associated with neurocognitive toxicity, which may compromise clinical outcomes. Older individuals are at increased risk for drug toxicity and clinical outcomes may be worse in older age, particularly among those individuals with cytochrome P450 (CYP) 2B6 polymorphisms associated with slower efavirenz metabolism. The aim of this study was to determine if the CYP2B6 polymorphisms differentially impacts loss to care in older people. Read More

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http://link.springer.com/10.1007/s13318-018-0507-5
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http://dx.doi.org/10.1007/s13318-018-0507-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420397PMC
April 2019
23 Reads

Evaluation of Drug Biliary Excretion Using Sandwich-Cultured Human Hepatocytes.

Eur J Drug Metab Pharmacokinet 2019 Feb;44(1):13-30

Centre de Recherche en Pharmacocinétique, Technologie Servier, 45000, Orléans, France.

Evaluation of hepatobiliary transport of drugs is an important challenge, notably during the development of new molecular identities. In this context, sandwich-cultured human hepatocytes (SCHH) have been proposed as an interesting and integrated tool for predicting in vitro biliary excretion of drugs. The present review was therefore designed to summarize key findings about SCHH, including their establishment, their main functional features and their use for the determination of canalicular transport and the prediction of in vivo biliary clearance and hepatobiliary excretion-related drug-drug interactions. Read More

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http://dx.doi.org/10.1007/s13318-018-0502-xDOI Listing
February 2019
28 Reads

Clinical Pharmacokinetics and Pharmacodynamics of Direct Oral Anticoagulants in Patients with Renal Failure.

Authors:
Roberto Padrini

Eur J Drug Metab Pharmacokinet 2019 Feb;44(1):1-12

Dipartimento di Medicina DIMED, Università degli Studi di Padova, Via Giustiniani 2, 35128, Padua, Italy.

A recent survey on the use of direct oral anticoagulants (DOACs) revealed that 43% of patients with atrial fibrillation and renal impairment were potentially overdosed and had a hazard ratio for major bleeding of 2.19. In this review, we analyse and discuss the effect of renal failure on the pharmacokinetics and pharmacodynamics of DOACs and of strategies proposed to adjust doses according to the level of renal dysfunction. Read More

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http://link.springer.com/10.1007/s13318-018-0501-y
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http://dx.doi.org/10.1007/s13318-018-0501-yDOI Listing
February 2019
10 Reads

Effect of CYP2C9 Polymorphisms on the Pharmacokinetics of Indomethacin During Pregnancy.

Eur J Drug Metab Pharmacokinet 2019 Feb;44(1):83-89

Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, 77555, USA.

Background And Objective: Cytochrome P450 (CYP) 2C9 catalyzes the biotransformation of indomethacin to its inactive metabolite O-desmethylindomethacin (DMI). The aim of this work was to determine the effect of CYP2C9 polymorphisms on indomethacin metabolism in pregnant women.

Methods: Plasma concentrations of indomethacin and DMI at steady state were analyzed with a validated LC-MS/MS method. Read More

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http://link.springer.com/10.1007/s13318-018-0505-7
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http://dx.doi.org/10.1007/s13318-018-0505-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6380929PMC
February 2019
26 Reads