2,898 results match your criteria Clinical pharmacokinetics[Journal]


Impact of Ethnicity-Specific Hepatic Microsomal Scaling Factor, Liver Weight, and Cytochrome P450 (CYP) 1A2 Content on Physiologically Based Prediction of CYP1A2-Mediated Pharmacokinetics in Young and Elderly Chinese Adults.

Clin Pharmacokinet 2019 Feb 15. Epub 2019 Feb 15.

Department of Pharmaceutics, College of Pharmacy, University of Florida, 1345 Center Drive, P3-27, Gainesville, FL, 32610-0494, USA.

Background: The vast majority of physiological and biological data required for physiologically based predictions are primarily available in Caucasians rather than other ethnic populations, which leads to a lack of confidence in the application of physiologically based pharmacokinetic (PBPK) modeling for ethnicity-specific prediction of pharmacokinetics in the Chinese population.

Objectives: In this study we recalibrate the system parameters of Chinese-specific PBPK modeling and explore for the first time the relative importance of ethnicity-specific microsomal protein per gram of liver (MPPGL), liver weight, and cytochrome P450 (CYP) 1A2 abundance to the projection of drug disposition mediated by CYP1A2 in young and elderly Chinese adults.

Methods: Chinese MPPGL levels and associated variability were parameterized and incorporated for the first time into ethnicity-specific PBPK models for the Chinese adults. Read More

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http://dx.doi.org/10.1007/s40262-019-00737-5DOI Listing
February 2019

Pharmacology, Pharmacokinetics and Pharmacodynamics of Eculizumab, and Possibilities for an Individualized Approach to Eculizumab.

Clin Pharmacokinet 2019 Feb 13. Epub 2019 Feb 13.

Department of Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.

Eculizumab is the first drug approved for the treatment of complement-mediated diseases, and current dosage schedules result in large interindividual drug concentrations. This review provides insight into the pharmacokinetic and pharmacodynamic properties of eculizumab, both for reported on-label (paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis) and off-label (hematopoietic stem cell transplantation-associated thrombotic microangiopathy) indications. Furthermore, we discuss the potential of therapeutic drug monitoring to individualize treatment and reduce costs. Read More

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http://link.springer.com/10.1007/s40262-019-00742-8
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http://dx.doi.org/10.1007/s40262-019-00742-8DOI Listing
February 2019
4 Reads

Physiologically Based Pharmacokinetic Modelling for First-In-Human Predictions: An Updated Model Building Strategy Illustrated with Challenging Industry Case Studies.

Clin Pharmacokinet 2019 Feb 7. Epub 2019 Feb 7.

Pharmaceutical Sciences, Roche Pharma Research and Early Development, Roche Innovation Centre Basel, Basel, Switzerland.

Physiologically based pharmacokinetic modelling is well established in the pharmaceutical industry and is accepted by regulatory agencies for the prediction of drug-drug interactions. However, physiologically based pharmacokinetic modelling is valuable to address a much wider range of pharmaceutical applications, and a new regulatory impact is expected as its full power is leveraged. As one example, physiologically based pharmacokinetic modelling is already routinely used during drug discovery for in-vitro to in-vivo translation and pharmacokinetic modelling in preclinical species, and this leads to the application of verified models for first-in-human pharmacokinetic predictions. Read More

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http://dx.doi.org/10.1007/s40262-019-00741-9DOI Listing
February 2019

Voriconazole: A Review of Population Pharmacokinetic Analyses.

Clin Pharmacokinet 2019 Jan 28. Epub 2019 Jan 28.

Department of Clinical Pharmacology, Translational Medicine Research Center, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, No. 261 Huansha Road, Hangzhou, 310006, China.

Numerous population pharmacokinetic studies on voriconazole have been conducted in recent years. This review aimed to comprehensively summarize the population pharmacokinetic models for voriconazole and to determine which covariates have been identified and which remain to be explored. We searched the PubMed and EMBASE databases from inception to March 2018 for population pharmacokinetic analyses of voriconazole using the nonlinear mixed-effect method. Read More

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http://dx.doi.org/10.1007/s40262-019-00735-7DOI Listing
January 2019
1 Read
5.053 Impact Factor

Physiologically Based Pharmacokinetic Modelling of Hyperforin to Predict Drug Interactions with St John's Wort.

Clin Pharmacokinet 2019 Jan 24. Epub 2019 Jan 24.

The University of Sydney, Sydney Pharmacy School, Pharmacy and Bank Building (A15), Camperdown, NSW, 2006, Australia.

Background And Objectives: Herb-drug interactions with St John's wort (SJW) have been widely studied in numerous clinical studies. The objective of this study was to develop and evaluate a physiologically based pharmacokinetic (PBPK) model for hyperforin (the constituent of SJW responsible for interactions), which has the potential to provide unique insights into SJW interactions and allow prediction of the likely extent of interactions with SJW compared to published interaction reports.

Methods: A PBPK model of hyperforin accounting for the induction of cytochrome P450 (CYP) 3A, CYP2C9 and CYP2C19 was developed in the Simcyp Simulator (version 17) and verified using published, clinically observed pharmacokinetic data. Read More

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http://dx.doi.org/10.1007/s40262-019-00736-6DOI Listing
January 2019

Personalized Tuberculosis Treatment Through Model-Informed Dosing of Rifampicin.

Clin Pharmacokinet 2019 Jan 23. Epub 2019 Jan 23.

Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.

Background And Objective: This study proposes a model-informed approach for therapeutic drug monitoring (TDM) of rifampicin to improve tuberculosis (TB) treatment.

Methods: Two datasets from pulmonary TB patients were used: a pharmacokinetic study (34 patients, 373 samples), and TDM data (96 patients, 391 samples) collected at Radboud University Medical Center, The Netherlands. Nine suitable population pharmacokinetic models of rifampicin were identified in the literature and evaluated on the datasets. Read More

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http://dx.doi.org/10.1007/s40262-018-00732-2DOI Listing
January 2019

Vancomycin Pharmacokinetics Throughout Life: Results from a Pooled Population Analysis and Evaluation of Current Dosing Recommendations.

Clin Pharmacokinet 2019 Jan 17. Epub 2019 Jan 17.

Department of Anesthesiology, University Medical Center Groningen, University of Groningen, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.

Background And Objectives: Uncertainty exists regarding the optimal dosing regimen for vancomycin in different patient populations, leading to a plethora of subgroup-specific pharmacokinetic models and derived dosing regimens. We aimed to investigate whether a single model for vancomycin could be developed based on a broad dataset covering the extremes of patient characteristics. Furthermore, as a benchmark for current dosing recommendations, we evaluated and optimised the expected vancomycin exposure throughout life and for specific patient subgroups. Read More

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http://dx.doi.org/10.1007/s40262-018-0727-5DOI Listing
January 2019
1 Read

Updated Clinical Pharmacokinetics and Pharmacodynamics of Oxycodone.

Clin Pharmacokinet 2019 Jan 17. Epub 2019 Jan 17.

Anaesthesiology and Intensive Care, Kuopio University Hospital, PO Box 100, 70029 KYS, Kuopio, Finland.

Global oxycodone consumption has increased sharply during the last two decades, and, in 2008, oxycodone consumption surpassed that of morphine. As oxycodone was synthesized in 1916 and taken to clinical use a year later, it has not undergone the same approval process required by today's standards. Most of the basic oxycodone pharmacokinetic (PK) data are from the 1990s and from academic research; however, a lot of additional data have been published over the last 10 years. Read More

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http://dx.doi.org/10.1007/s40262-018-00731-3DOI Listing
January 2019
4 Reads

Developmental Pharmacokinetics and Age-Appropriate Dosing Design of Milrinone in Neonates and Infants with Acute Kidney Injury Following Cardiac Surgery.

Clin Pharmacokinet 2019 Jan 3. Epub 2019 Jan 3.

Division of Clinical Pharmacology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC6018, Cincinnati, OH, 45229-3039, USA.

Background And Objective: Milrinone is used for the prevention of low cardiac output syndrome in pediatric patients after cardiac surgery. Milrinone is mainly eliminated by the kidneys; however, there is limited information on milrinone pharmacokinetics in infants who have acute kidney injury (AKI). The aim of this study was to develop a milrinone population pharmacokinetic model in neonates and infants with or without AKI. Read More

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http://link.springer.com/10.1007/s40262-018-0729-3
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http://dx.doi.org/10.1007/s40262-018-0729-3DOI Listing
January 2019
3 Reads

Lack of Effect of 12-Week Treatment with Risankizumab on the Pharmacokinetics of Cytochrome P450 Probe Substrates in Patients with Moderate to Severe Chronic Plaque Psoriasis.

Clin Pharmacokinet 2018 Dec 21. Epub 2018 Dec 21.

Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.

Objective: The objective of this study was to characterize the effects of risankizumab on the in vivo activity of cytochrome P450 (CYP) 1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A in psoriasis patients using a cocktail approach.

Methods: Patients with moderate to severe chronic plaque psoriasis (n = 21) received single oral doses of sensitive probe substrates for CYP1A2 (caffeine 100 mg), CYP2C9 (warfarin 10 mg), CYP2C19 (omeprazole 20 mg), CYP2D6 (metoprolol 50 mg), and CYP3A (midazolam 2 mg) on day 1, followed by 12 weeks of subcutaneous risankizumab treatment of 150 mg once every 4 weeks from day 8 to day 92, and again the same cocktail of substrates on day 98. Serial blood samples were collected for determination of the CYP probe drugs and metabolites with and without risankizumab. Read More

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http://dx.doi.org/10.1007/s40262-018-0730-xDOI Listing
December 2018
6 Reads

Safety and Pharmacokinetics of Single and Multiple Ascending Doses of the Novel Oral Human GLP-1 Analogue, Oral Semaglutide, in Healthy Subjects and Subjects with Type 2 Diabetes.

Clin Pharmacokinet 2018 Dec 18. Epub 2018 Dec 18.

Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.

Background: Oral semaglutide is a novel tablet containing the human glucagon-like peptide-1 (GLP‑1) analogue semaglutide, co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). The safety and pharmacokinetics of oral semaglutide were investigated in two randomised, double-blind, placebo-controlled trials.

Methods: In a single-dose, first-in-human trial, 135 healthy males received oral semaglutide (2-20 mg semaglutide co-formulated with 150-600 mg SNAC) or placebo with SNAC. Read More

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http://dx.doi.org/10.1007/s40262-018-0728-4DOI Listing
December 2018
1 Read

Correction to: Clinical Pharmacokinetics and Dose Recommendations for Posaconazole in Infants and Children.

Clin Pharmacokinet 2019 Jan;58(1):141

Infection, Inflammation, Immunity Section, Room 661, UCL Great Ormond Street Institute of Child Health, University College London, London, WC1N 1EH, UK.

However, the Original article has been updated with the Open Access under Commercial License. Read More

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http://dx.doi.org/10.1007/s40262-018-0722-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325978PMC
January 2019
2 Reads

Correction to: Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance.

Clin Pharmacokinet 2019 Jan;58(1):139

Infection, Inflammation and Rheumatology Section, UCL Great Ormond Street Institute of Child Heath, University College London, London, UK.

The article Pharmacokinetic-Pharmacodynamic Modeling in Pediatric Drug Development, and the Importance of Standardized Scaling of Clearance Written by Eva Germovsek,Charlotte I. S. Barker, Mike Sharland, Joseph F. Read More

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http://dx.doi.org/10.1007/s40262-018-0723-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325981PMC
January 2019
1 Read

Population Pharmacokinetics of the BTK Inhibitor Acalabrutinib and its Active Metabolite in Healthy Volunteers and Patients with B-Cell Malignancies.

Clin Pharmacokinet 2018 Dec 17. Epub 2018 Dec 17.

Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, Boston, MA, USA.

Introduction: Bruton tyrosine kinase (BTK) is a key component of B-cell receptor signalling, critical for cell proliferation. Acalabrutinib, a selective, covalent BTK inhibitor, recently received an accelerated approval in relapsed/refractory mantle cell lymphoma. This analysis characterized the population pharmacokinetics (PK) of acalabrutinib and its metabolite ACP-5862. Read More

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http://dx.doi.org/10.1007/s40262-018-0725-7DOI Listing
December 2018
2 Reads

Correction to: Pharmacokinetic and Pharmacodynamic Modeling to Optimize the Dose of Vestronidase Alfa, an Enzyme Replacement Therapy for Treatment of Patients with Mucopolysaccharidosis Type VII: Results from Three Trials.

Clin Pharmacokinet 2018 Dec 4. Epub 2018 Dec 4.

Ultragenyx Pharmaceutical Inc., 60 Leveroni Court, Novato, CA, 94949, USA.

Introduction section, para 3, lines 2-4 which previously read. Read More

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http://dx.doi.org/10.1007/s40262-018-0726-6DOI Listing
December 2018
1 Read

Pharmacokinetic and Pharmacodynamic Modeling to Optimize the Dose of Vestronidase Alfa, an Enzyme Replacement Therapy for Treatment of Patients with Mucopolysaccharidosis Type VII: Results from Three Trials.

Clin Pharmacokinet 2018 Nov 23. Epub 2018 Nov 23.

Ultragenyx Pharmaceutical Inc., 60 Leveroni Court, Novato, CA, 94949, USA.

Introduction: Mucopolysaccharidosis type VII (MPS VII, Sly Syndrome) is a progressive, debilitating, ultra-rare lysosomal storage disorder caused by the deficiency of β-glucuronidase (GUS), an enzyme required for breakdown of glycosaminoglycans (GAGs). Vestronidase alfa, a recombinant human GUS, is an enzyme replacement therapy approved in the US and EU for the treatment of MPS VII.

Methods: The pharmacokinetics (PK) and pharmacodynamics (PD) of vestronidase alfa were evaluated in 23 adult and pediatric subjects with MPS VII enrolled in phase I-III clinical trials to optimize the clinical dosing regimen of vestronidase alfa. Read More

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http://dx.doi.org/10.1007/s40262-018-0721-yDOI Listing
November 2018
9 Reads

Pharmacogenetics of Membrane Transporters of Tacrolimus in Solid Organ Transplantation.

Clin Pharmacokinet 2018 Nov 10. Epub 2018 Nov 10.

Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre, Rennes University Hospital, Rennes, France.

Membrane transporters play an essential role in the pharmacokinetics of drugs as they mediate exchanges between biological compartments. Tacrolimus is characterized by wide interpatient variability in terms of its pharmacokinetics that may in part be due to genetic factors. The pharmacogenetics of drug transporters is therefore a promising area to explore in the clinical pharmacology of tacrolimus. Read More

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http://dx.doi.org/10.1007/s40262-018-0717-7DOI Listing
November 2018
18 Reads

A Systematic Review on the Effect of HIV Infection on the Pharmacokinetics of First-Line Tuberculosis Drugs.

Clin Pharmacokinet 2018 Nov 8. Epub 2018 Nov 8.

Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, PO Box 30.001, 9700 RB, Groningen, The Netherlands.

Introduction: Contrasting findings have been published regarding the effect of human immunodeficiency virus (HIV) on tuberculosis (TB) drug pharmacokinetics (PK).

Objectives: The aim of this systematic review was to investigate the effect of HIV infection on the PK of the first-line TB drugs (FLDs) rifampicin, isoniazid, pyrazinamide and ethambutol by assessing all published literature.

Methods: Searches were performed in MEDLINE (through PubMed) and EMBASE to find original studies evaluating the effect of HIV infection on the PK of FLDs. Read More

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http://link.springer.com/10.1007/s40262-018-0716-8
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http://dx.doi.org/10.1007/s40262-018-0716-8DOI Listing
November 2018
8 Reads

Interactions Between Antiepileptic and Antibiotic Drugs: A Systematic Review and Meta-Analysis with Dosing Implications.

Clin Pharmacokinet 2018 Nov 7. Epub 2018 Nov 7.

Unit of Clinical Pharmacology, Department of Biomedical and Clinical Sciences L. Sacco, "Luigi Sacco" University Hospital, Università di Milano, Via GB Grassi 74, 20157, Milan, Italy.

Introduction: Qualitative studies on drug-drug interactions (DDIs) between anticonvulsants and antibiotics report pharmacokinetic changes that may increase the clinical risks in terms of adverse drug reactions (ADRs) and efficacy. However, no studies have provided a systematic and quantitative analysis of anticonvulsant-antibiotic pharmacokinetic DDIs. To provide such indications, we systematically and critically reviewed the literature on anticonvulsant-antibiotic DDIs in terms of quantitative pharmacokinetic changes and related ADRs. Read More

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http://dx.doi.org/10.1007/s40262-018-0720-zDOI Listing
November 2018
17 Reads

Clinical Pharmacology of Fast-Acting Insulin Aspart Versus Insulin Aspart Measured as Free or Total Insulin Aspart and the Relation to Anti-Insulin Aspart Antibody Levels in Subjects with Type 1 Diabetes Mellitus.

Clin Pharmacokinet 2018 Nov 7. Epub 2018 Nov 7.

Profil, Hellersbergstrasse 9, 41460, Neuss, Germany.

Background: Fast-acting insulin aspart (faster aspart) is an ultra-fast-acting formulation of insulin aspart (IAsp). This post hoc analysis investigated the pharmacokinetics of faster aspart versus IAsp, measured as free or total IAsp, and the relationship between anti-IAsp antibodies and the pharmacokinetics/pharmacodynamics of faster aspart and IAsp.

Methods: Free and total IAsp concentrations and anti-IAsp antibodies were determined in adults with type 1 diabetes mellitus receiving subcutaneous faster aspart and/or IAsp in four single-dose clinical pharmacology trials (n = 175) and a 26-week phase IIIa trial (n = 1040). Read More

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http://dx.doi.org/10.1007/s40262-018-0718-6DOI Listing
November 2018
13 Reads

Impact of CYP3A4*22 on Pazopanib Pharmacokinetics in Cancer Patients.

Clin Pharmacokinet 2018 Oct 27. Epub 2018 Oct 27.

Department of Medical Oncology, Erasmus MC Cancer Institute, Josephine Nefkens Building, Room Be-424, PO Box 5201, 3008 AE, Rotterdam, The Netherlands.

Background And Objective: As pazopanib plasma trough concentrations are correlated with treatment outcome, we explored whether single nucleotide polymorphisms in the elimination pathway of pazopanib affect systemic pazopanib concentrations.

Methods: The decreased function alleles CYP3A4 15389 C > T (*22), ABCB1 3435 C >T, ABCG2 421 C >A, and ABCG2 34G >A were analyzed within a recently developed population-pharmacokinetic model.

Results: Incorporation of CYP3A4*22 in the model resulted in a 35% lower clearance for variant carriers (0. Read More

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http://link.springer.com/10.1007/s40262-018-0719-5
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http://dx.doi.org/10.1007/s40262-018-0719-5DOI Listing
October 2018
8 Reads

Bridging Olaparib Capsule and Tablet Formulations Using Population Pharmacokinetic Meta-analysis in Oncology Patients.

Clin Pharmacokinet 2018 Oct 24. Epub 2018 Oct 24.

Quantitative Clinical Pharmacology, Early Clinical Development, IMED Biotech Unit, AstraZeneca, 35 Gatehouse Drive, Boston, MA, 02451, USA.

Background: Olaparib is a first-in-class potent oral poly(ADP-ribose) polymerase inhibitor.

Objectives: The aims of this analysis were to establish an integrated population pharmacokinetic (PK) model of olaparib in patients with solid tumors and to bridge the PK of olaparib between capsule and tablet formulations.

Methods: The population PK model was developed using plasma concentration data from 659 patients in 11 phase I, II, and III studies of olaparib tablets/capsules monotherapy. Read More

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http://link.springer.com/10.1007/s40262-018-0714-x
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http://dx.doi.org/10.1007/s40262-018-0714-xDOI Listing
October 2018
26 Reads

Population Pharmacokinetics of Fludarabine in Children and Adults during Conditioning Prior to Allogeneic Hematopoietic Cell Transplantation.

Clin Pharmacokinet 2018 Oct 17. Epub 2018 Oct 17.

Department of Pharmacy and Pharmacology, Antoni van Leeuwenhoek Hospital/Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background: Fludarabine is often used as an important drug in reduced toxicity conditioning regimens prior to hematopoietic cell transplantation (HCT). As no definitive pharmacokinetic (PK) basis for HCT dosing for the wide age and weight range in HCT is available, linear body surface area (BSA)-based dosing is still used.

Objective: We sought to describe the population PK of fludarabine in HCT recipients of all ages. Read More

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http://dx.doi.org/10.1007/s40262-018-0715-9DOI Listing
October 2018
3 Reads

Cardiovascular Risk Management and Hepatitis C: Combining Drugs.

Clin Pharmacokinet 2018 Sep 27. Epub 2018 Sep 27.

Department of Pharmacy, Radboud university medical center, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands.

Direct-acting antivirals (DAAs) are known victims (substrate) and perpetrators (cause) of drug-drug interactions (DDIs). These DAAs are used for the treatment of hepatitis C virus (HCV) infections and are highly effective drugs. Drugs used for cardiovascular risk management are frequently used by HCV-infected patients, whom also are treated with DAAs. Read More

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http://dx.doi.org/10.1007/s40262-018-0710-1DOI Listing
September 2018
3 Reads

Pharmacokinetics of Hydroxychloroquine in Pregnancies with Rheumatic Diseases.

Clin Pharmacokinet 2018 Sep 25. Epub 2018 Sep 25.

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA.

Background: Hydroxychloroquine is an oral drug prescribed to pregnant women with rheumatic disease to reduce disease activity and prevent flares. Physiologic changes during pregnancy may substantially alter drug pharmacokinetics. However, the effect of pregnancy on hydroxychloroquine disposition and the potential need for dose adjustment remains virtually unknown. Read More

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http://link.springer.com/10.1007/s40262-018-0712-z
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http://dx.doi.org/10.1007/s40262-018-0712-zDOI Listing
September 2018
18 Reads

Comprehensive Measurements of Intrauterine and Postnatal Exposure to Lamotrigine.

Clin Pharmacokinet 2018 Sep 25. Epub 2018 Sep 25.

Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, 52074, Aachen, Germany.

Objective: The aim of this study was to measure and investigate correlations of lamotrigine concentrations in maternal as well as umbilical cord blood, amniotic fluid, and breast milk to account for the distribution of the drug.

Methods: Concentrations of lamotrigine were measured in 19 mother-infant pairs at the time of delivery. To account for the penetration ratio into amniotic fluid, cord blood and breast milk, the concentration of lamotrigine in the particular environment was divided by the concentration in maternal serum. Read More

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http://dx.doi.org/10.1007/s40262-018-0713-yDOI Listing
September 2018
2 Reads

A Generic Model for Quantitative Prediction of Interactions Mediated by Efflux Transporters and Cytochromes: Application to P-Glycoprotein and Cytochrome 3A4.

Clin Pharmacokinet 2018 Sep 8. Epub 2018 Sep 8.

Pharmacie, Groupement Hospitalier Nord, Hospices Civils de Lyon, Lyon, France.

Background And Objective: The In Vivo Mechanistic Static Model (IMSM) is a powerful method used to predict the magnitude of drug-drug interactions (DDIs) mediated by cytochromes. The objective of this study was to extend the IMSM paradigm to DDIs mediated by efflux transporters and cytochromes.

Methods: First, a generic model for this kind of interaction was devised. Read More

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http://link.springer.com/10.1007/s40262-018-0711-0
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http://dx.doi.org/10.1007/s40262-018-0711-0DOI Listing
September 2018
12 Reads

Monitoring of Tobramycin Exposure: What is the Best Estimation Method and Sampling Time for Clinical Practice?

Clin Pharmacokinet 2019 Mar;58(3):389-399

School of Pharmacy, Pharmacy Australia Centre of Excellence, University of Queensland, 20 Cornwall Street, Woolloongabba, Brisbane, QLD, 4102, Australia.

Objectives: The objective of this article is to investigate the influence of blood sampling times on tobramycin exposure estimation and clinical decisions and to determine the best sampling times for two estimation methods used for therapeutic drug monitoring.

Methods: Adult patients with cystic fibrosis, treated with once-daily intravenous tobramycin, were intensively sampled over one 24-h dosing interval to determine true exposure (AUC). The AUCs were then estimated using both log-linear regression and Bayesian forecasting methods for 21 different sampling time combinations. Read More

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http://link.springer.com/10.1007/s40262-018-0707-9
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http://dx.doi.org/10.1007/s40262-018-0707-9DOI Listing
March 2019
12 Reads

Repository Describing an Aging Population to Inform Physiologically Based Pharmacokinetic Models Considering Anatomical, Physiological, and Biological Age-Dependent Changes.

Clin Pharmacokinet 2018 Aug 21. Epub 2018 Aug 21.

Division of Infectious Diseases and Hospital Epidemiology, Departments of Medicine and Clinical Research, University Hospital Basel, Basel, Switzerland.

Background: Aging is characterized by anatomical, physiological, and biological changes that can impact drug kinetics. The elderly are often excluded from clinical trials and knowledge about drug kinetics and drug-drug interaction magnitudes is sparse. Physiologically based pharmacokinetic modeling can overcome this clinical limitation but detailed descriptions of the population characteristics are essential to adequately inform models. Read More

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http://dx.doi.org/10.1007/s40262-018-0709-7DOI Listing
August 2018
4 Reads

Intra-monocyte Pharmacokinetics of Imiglucerase Supports a Possible Personalized Management of Gaucher Disease Type 1.

Clin Pharmacokinet 2018 Aug 21. Epub 2018 Aug 21.

Hématologie Biologique, CHU Clermont-Ferrand, CHU Estaing, 1 place Lucie et Raymond Aubrac, 63003, Clermont-Ferrand Cedex 1, France.

Background And Objectives: Intravenous imiglucerase enzyme replacement therapy for Gaucher disease type 1 administered every 2 weeks is at variance with the imiglucerase plasma half-life of a few minutes. We hypothesized that studying the pharmacokinetics of imiglucerase in blood Gaucher disease type 1 monocytes would be more relevant for understanding enzyme replacement therapy responses.

Methods: Glucocerebrosidase intra-monocyte activity was studied by flow cytometry. Read More

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http://link.springer.com/10.1007/s40262-018-0708-8
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http://dx.doi.org/10.1007/s40262-018-0708-8DOI Listing
August 2018
21 Reads

Population Pharmacokinetics of the Interleukin-23 Inhibitor Risankizumab in Subjects with Psoriasis and Crohn's Disease: Analyses of Phase I and II Trials.

Clin Pharmacokinet 2019 Mar;58(3):375-387

Clinical Pharmacology and Pharmacometrics, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL, 60064, USA.

Background And Objectives: Risankizumab is a humanized anti-interleukin-23 monoclonal antibody in development for the treatment of several inflammatory diseases. This work characterized the pharmacokinetics of risankizumab and evaluated covariates that may affect its exposures using phase I and II trial data in subjects with psoriasis and Crohn's disease.

Methods: Plasma concentration measurements from a phase I study and a phase II study in subjects with psoriasis (n = 157; single doses of 0. Read More

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http://dx.doi.org/10.1007/s40262-018-0704-zDOI Listing
March 2019
12 Reads

Clinical Pharmacology of Ixazomib: The First Oral Proteasome Inhibitor.

Clin Pharmacokinet 2018 Aug 17. Epub 2018 Aug 17.

Millennium Pharmaceuticals, Inc., a Wholly Owned Subsidiary of Takeda Pharmaceutical Company Limited, 40 Landsdowne Street, Cambridge, MA, 02139, USA.

Ixazomib, the first oral proteasome inhibitor, is approved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. Ixazomib is a selective, potent, and reversible inhibitor of the 20S proteasome, and preferentially binds to and inhibits the β5 chymotrypsin-like proteolytic site. Ixazomib absorption is rapid, with a median time to reach maximum plasma concentration of approximately 1 h post-dose. Read More

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http://link.springer.com/10.1007/s40262-018-0702-1
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http://dx.doi.org/10.1007/s40262-018-0702-1DOI Listing
August 2018
4 Reads

Clinical Pharmacokinetics and Pharmacodynamics of Ceftazidime-Avibactam Combination: A Model-Informed Strategy for its Clinical Development.

Clin Pharmacokinet 2018 Aug 11. Epub 2018 Aug 11.

Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.

Avibactam is a non-β-lactam, β-lactamase inhibitor of the diazabicyclooctane class that covalently acylates its β-lactamase targets, encompassing extended spectrum of activities that cover serine β-lactamases but not metallo-β-lactamases. Ceftazidime and avibactam have complementary pharmacokinetic (PK) profiles. Both drugs have a half-life of approximately 2 h, making them suitable to be combined in a fixed-dose combination ratio of 4:1 (ceftazidime:avibactam). Read More

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http://dx.doi.org/10.1007/s40262-018-0705-yDOI Listing
August 2018
18 Reads

A Robust Statistical Approach to Analyse Population Pharmacokinetic Data in Critically Ill Patients Receiving Renal Replacement Therapy.

Clin Pharmacokinet 2019 Feb;58(2):263-270

Clinical Trials and Biostatistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Background And Aim: Current approaches to antibiotic dose determination in critically ill patients requiring renal replacement therapy are primarily based on the assessment of highly heterogeneous data from small number of patients. The standard modelling approaches limit the scope of constructing robust confidence boundaries of the distribution of pharmacokinetics (PK) parameters, especially when the evaluation of possible association of demographic and clinical factors at different levels of the distribution of drug clearance is of interest. Commonly used compartmental models generally construct the inferences through a linear or non-linear mean regression, which is inadequate when the distribution is skewed, multi-modal or effected by atypical observation. Read More

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http://dx.doi.org/10.1007/s40262-018-0690-1DOI Listing
February 2019
9 Reads

Clinical Pharmacokinetics and Pharmacodynamics of Dabrafenib.

Clin Pharmacokinet 2018 Aug 9. Epub 2018 Aug 9.

UMR8638 CNRS, Faculty of Pharmacy, University Paris Descartes, PRES Sorbonne Paris Cité, Paris, France.

Dabrafenib is a potent and selective inhibitor of BRAF-mutant kinase that is approved, as monotherapy or in combination with trametinib (mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor), for unresectable or metastatic BRAF-mutated melanoma, advanced non-small cell lung cancer and anaplastic thyroid cancer harbouring the BRAF mutation. The recommended dose of dabrafenib is 150 mg twice daily (bid) under fasted conditions. After single oral administration of the recommended dose, the absolute oral bioavailability (F) of dabrafenib is 95%. Read More

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http://link.springer.com/10.1007/s40262-018-0703-0
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http://dx.doi.org/10.1007/s40262-018-0703-0DOI Listing
August 2018
15 Reads

Population-Pharmacokinetic and Covariate Analysis of Lurbinectedin (PM01183), a New RNA Polymerase II Inhibitor, in Pooled Phase I/II Trials in Patients with Cancer.

Clin Pharmacokinet 2019 Mar;58(3):363-374

Department of Clinical Pharmacology, PharmaMar, S.A., Avda. de los Reyes, 1 Colmenar Viejo, 28770, Madrid, Spain.

Background And Objectives: Lurbinectedin is an inhibitor of RNA polymerase II currently under clinical development for intravenous administration as a single agent and in combination with other anti-tumor agents for the treatment of several tumor types. The objective of this work was to develop a population-pharmacokinetic model in this patient setting and to elucidate the main predictors to guide the late stages of development.

Methods: Data from 443 patients with solid and hematologic malignancies treated in six phase I and three phase II trials with lurbinectedin as a single agent or combined with other agents were included in the analysis. Read More

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http://dx.doi.org/10.1007/s40262-018-0701-2DOI Listing
March 2019
23 Reads

Effect of Fluconazole Coadministration and CYP2C9 Genetic Polymorphism on Siponimod Pharmacokinetics in Healthy Subjects.

Clin Pharmacokinet 2019 Mar;58(3):349-361

Novartis Institutes for BioMedical Research (NIBR), 4002, Basel, Switzerland.

Objectives: The aim of this study was to assess the pharmacokinetics (PK) and safety/tolerability of siponimod in healthy subjects when coadministered with (1) the moderate cytochrome P450 (CYP) 2C9 and CYP3A inhibitor fluconazole (Study A), and (2) with three different CYP2C9 genotype variants (Study B).

Methods: Study A was an open-label, single-dose study comprising periods 1 (14 days; day 1: siponimod 4 mg) and 2 (20 days; day 1: fluconazole 200 mg twice daily; days 2-19: fluconazole 200 mg once daily; day 3: siponimod 4 mg) in healthy subjects (n = 14) with the wild-type CYP2C9 genotype (CYP2C9*1/*1). Study B was a multicentre, open-label study comprising parts 1 (day 1: siponimod 0. Read More

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http://dx.doi.org/10.1007/s40262-018-0700-3DOI Listing
March 2019
4 Reads
5.053 Impact Factor

Correction to: The Clinical Pharmacology of Cladribine Tablets for the Treatment of Relapsing Multiple Sclerosis.

Clin Pharmacokinet 2019 Mar;58(3):401

Merck Institute for Pharmacometrics, Merck Serono S.A., Switzerland, an Affiliate of Merck KGaA, Darmstadt, Germany.

The cladribine prodrug is phosphorylated intracellularly to its active product, 2-chlorodeoxyadenosine triphosphate (Cd-ATP), by deoxycytidine kinase. Read More

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http://dx.doi.org/10.1007/s40262-018-0706-xDOI Listing
March 2019
3 Reads

Population Pharmacokinetic Modeling of Gemtuzumab Ozogamicin in Adult Patients with Acute Myeloid Leukemia.

Clin Pharmacokinet 2019 Mar;58(3):335-347

Pfizer Inc., 10555 Science Center Drive, 2405, San Diego, CA, 92121, USA.

Background And Objective: Gemtuzumab ozogamicin is an antibody-drug conjugate composed of the anti-CD33 monoclonal antibody hP67.6 covalently linked to N-acetyl-gamma-calicheamicin dimethylhydrazide, a potent cytotoxic antibiotic. The aim of this study was to characterize the population pharmacokinetics of gemtuzumab ozogamicin, represented by total hP67. Read More

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http://dx.doi.org/10.1007/s40262-018-0699-5DOI Listing
March 2019
2 Reads

Population Pharmacokinetics of Gemtuzumab Ozogamicin in Pediatric Patients with Relapsed or Refractory Acute Myeloid Leukemia.

Clin Pharmacokinet 2019 Feb;58(2):271-282

Clinical Pharmacology, Oncology, Global Product Development, Pfizer Inc, 10555 Science Center Drive, San Diego, CA, 92121, USA.

Background And Objective: To date, the population pharmacokinetics (popPK) of gemtuzumab ozogamicin (GO), a CD33-directed antibody-drug conjugate consisting of hP67.6 antibody linked to N-acetyl gamma calicheamicin used in the treatment of acute myeloid leukemia (AML), has not been characterized in pediatric patients. This report describes the popPK of GO following intravenous administration in 29 pediatric patients aged ≤ 17 years with relapsed or refractory AML who were enrolled in the 0903A1-102-US phase I/II study. Read More

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http://link.springer.com/10.1007/s40262-018-0694-x
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http://dx.doi.org/10.1007/s40262-018-0694-xDOI Listing
February 2019
20 Reads

Clinical Pharmacokinetics and Pharmacodynamics of Propofol.

Clin Pharmacokinet 2018 Dec;57(12):1539-1558

Department of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.

Propofol is an intravenous hypnotic drug that is used for induction and maintenance of sedation and general anaesthesia. It exerts its effects through potentiation of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) at the GABA receptor, and has gained widespread use due to its favourable drug effect profile. The main adverse effects are disturbances in cardiopulmonary physiology. Read More

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http://link.springer.com/10.1007/s40262-018-0672-3
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http://dx.doi.org/10.1007/s40262-018-0672-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6267518PMC
December 2018
22 Reads

Effects of Postponing Treatment in the Second Year of Cladribine Administration: Clinical Trial Simulation Analysis of Absolute Lymphocyte Counts and Relapse Rate in Patients with Relapsing-Remitting Multiple Sclerosis.

Clin Pharmacokinet 2018 Jul 11. Epub 2018 Jul 11.

Quantitative Pharmacology, Merck Institute for Pharmacometrics, Merck Serono S.A., EPFL Innovation Park - Building I, CH-1015, Lausanne, Switzerland.

Introduction: Cladribine Tablets (MAVENCLAD) selectively reduce absolute lymphocyte counts (ALCs) in patients with multiple sclerosis. The recommended cumulative dose of Cladribine Tablets is 3.5 mg/kg over 4-5 days in months 1 and 2 of treatment years 1 and 2, followed by prolonged efficacy with no additional treatment. Read More

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http://dx.doi.org/10.1007/s40262-018-0693-yDOI Listing
July 2018
2 Reads

The Clinical Pharmacology of Cladribine Tablets for the Treatment of Relapsing Multiple Sclerosis.

Clin Pharmacokinet 2019 Mar;58(3):283-297

Merck Institute for Pharmacometrics, Merck Serono S.A., Switzerland, an Affiliate of Merck KGaA, Darmstadt, Germany.

Cladribine Tablets (MAVENCLAD) are used to treat relapsing multiple sclerosis (MS). The recommended dose is 3.5 mg/kg, consisting of 2 annual courses, each comprising 2 treatment weeks 1 month apart. Read More

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http://link.springer.com/10.1007/s40262-018-0695-9
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http://dx.doi.org/10.1007/s40262-018-0695-9DOI Listing
March 2019
17 Reads

Fetal Physiologically Based Pharmacokinetic Models: Systems Information on the Growth and Composition of Fetal Organs.

Clin Pharmacokinet 2019 Feb;58(2):235-262

Certara UK Limited (Simcyp), Level 2-Acero, 1 Concourse Way, Sheffield, S1 2BJ, UK.

Background: The growth of fetal organs is a dynamic process involving considerable changes in the anatomical and physiological parameters that can alter fetal exposure to xenobiotics in utero. Physiologically based pharmacokinetic models can be used to predict the fetal exposure as time-varying parameters can easily be incorporated.

Objective: The objective of this study was to collate, analyse and integrate the available time-varying parameters needed for the physiologically based pharmacokinetic modelling of xenobiotic kinetics in a fetal population. Read More

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http://dx.doi.org/10.1007/s40262-018-0685-yDOI Listing
February 2019
8 Reads

Faster Insulin Aspart: A New Bolus Option for Diabetes Mellitus.

Clin Pharmacokinet 2018 Jul 6. Epub 2018 Jul 6.

Department of Pharmacy Practice, Presbyterian College School of Pharmacy, 307 North Broad Street, Clinton, SC, 29325, USA.

Since the approval of bolus insulin, it has been used frequently in clinical practice for the management of type 1 and 2 diabetes mellitus for postprandial control. Another new product is faster insulin aspart (Fiasp, Novo Nordisk), a fast-acting insulin with 100 units/mL. Several studies have been conducted evaluating the pharmacokinetics and pharmacodynamics of faster insulin aspart, compared with insulin aspart. Read More

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http://dx.doi.org/10.1007/s40262-018-0696-8DOI Listing
July 2018
6 Reads

Correction to: Clinical Pharmacokinetic Characteristics of Cebranopadol, a Novel First-in-Class Analgesic.

Clin Pharmacokinet 2018 Aug;57(8):1057-1058

Preclinical Drug Development-Pharmacokinetics, Grünenthal GmbH, Aachen, Germany.

For each simulation, PK profiles from 1000 subjects were simulated based on a titration scheme. Read More

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http://dx.doi.org/10.1007/s40262-018-0686-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6028882PMC
August 2018
4 Reads

Comment on van Rongen et al., "Higher Midazolam Clearance in Obese Adolescents Compared with Morbidly Obese Adults".

Clin Pharmacokinet 2018 Oct;57(10):1355

School of Pharmacy, University of Otago, Dunedin, New Zealand.

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http://dx.doi.org/10.1007/s40262-018-0691-0DOI Listing
October 2018
3 Reads

Author's Reply to Reith: "Higher Midazolam Clearance in Obese Adolescents Compared with Morbidly Obese Adults".

Clin Pharmacokinet 2018 Oct;57(10):1357-1358

Department of Clinical Pharmacy, St. Antonius Hospital, Nieuwegein, The Netherlands.

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http://dx.doi.org/10.1007/s40262-018-0692-zDOI Listing
October 2018
5 Reads