25,914 results match your criteria pharmacokinetic model

Tacrolimus Therapy in Adult Heart Transplant Recipients: Evaluation of a Bayesian Forecasting Software.

Ther Drug Monit 2021 Jun 8. Epub 2021 Jun 8.

St. Vincent's Clinical School, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia. Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, Sydney, NSW, Australia. Ministry of Health, Putrajaya, Malaysia. School of Pharmacy, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia. Kinghorn Centre for Clinical Genomics, Garvan Institute of Medical Research, Sydney, NSW, Australia. Department of Pharmacy, St. Vincent's Hospital, Sydney, NSW, Australia. School of Medical Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia.

Background: Therapeutic drug monitoring is recommended to guide tacrolimus dosing because of its narrow therapeutic window and considerable pharmacokinetic variability. This study assessed tacrolimus dosing and monitoring practices in heart transplant recipients and evaluated the predictive performance of a Bayesian forecasting software using a renal transplant-derived tacrolimus model to predict tacrolimus concentrations.

Methods: A retrospective audit of heart transplant recipients (n=87) treated with tacrolimus was performed. Read More

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Skin Pharmacokinetics of Transdermal Scopolamine: Measurements and Modeling.

Mol Pharm 2021 Jun 14. Epub 2021 Jun 14.

Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K.

Prediction of skin absorption and local bioavailability from topical formulations remains a difficult task. An important challenge in forecasting topical bioavailability is the limited information available about local and systemic drug concentrations post application of topical drug products. Commercially available transdermal patches, such as Scopoderm (Novartis Consumer Health UK), offer an opportunity to test these experimental approaches as systemic pharmacokinetic data are available with which to validate a predictive model. Read More

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Advances in Therapeutic Drug Monitoring in Biologic Therapies for Pediatric Inflammatory Bowel Disease.

Front Pediatr 2021 26;9:661536. Epub 2021 May 26.

Division of Pediatric Gastroenterology, Hepatology, and Nutrition, London Health Sciences Centre, Children's Hospital Western Ontario, Western University, London, ON, Canada.

In the current era of treat-to-target strategies, therapeutic drug monitoring (TDM) has emerged as a potential tool in optimizing the efficacy of biologics for children diagnosed with inflammatory bowel disease (IBD). The incorporation of TDM into treatment algorithms, however, has proven to be complex. "Proactive" TDM is emerging as a therapeutic strategy due to a recently published pediatric RCT showing a clear benefit of "proactive" TDM in anti-TNF therapy. Read More

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Using Liposomes to Alleviate the Toxicity of Chelerythrine, a Natural PKC Inhibitor, in Treating Non-Small Cell Lung Cancer.

Front Oncol 2021 27;11:658543. Epub 2021 May 27.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Aim Of The Study: CHE can inhibit the proliferation of lung cancer cells and induce apoptosis. However, despite having toxicity, CHE has not been thoroughly investigated in term of its antitumor effect. The present study evaluated the antitumor effect of CHE on non-small cell lung cancer cell line HCC827. Read More

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Population Pharmacokinetics of Ropeginterferon Alfa-2b: A Comparison Between Healthy Caucasian and Chinese Subjects.

Front Pharmacol 2021 28;12:673492. Epub 2021 May 28.

Department of Pharmacy, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

To develop a population pharmacokinetic (PK) model for ropeginterferon alfa-2b and to compare its PK properties between Caucasian and Chinese populations. A population PK model was developed based on data from two phase I clinical trials conducted in Caucasian and Chinese individuals, to evaluate the influence of ethnicity on the PKs of ropeginterferon alfa-2b. We included 456 observations from 30 healthy Caucasian subjects and 438 observations from 27 healthy Chinese subjects in the population PK analysis. Read More

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Bleomycin administered by laser-assisted drug delivery or intradermal needle-injection results in distinct biodistribution patterns in skin: investigations with mass spectrometry imaging.

Drug Deliv 2021 Dec;28(1):1141-1149

Department of Dermatology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark.

Bleomycin (BLM) is being repositioned in dermato-oncology for intralesional and intra-tumoural use. Although conventionally administered by local needle injections (NIs), ablative fractional lasers (AFLs) can facilitate topical BLM delivery. Adding local electroporation (EP) can augment intracellular uptake in the target tissue. Read More

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December 2021

Estimation of the risk of local and systemic effects in infants after ingestion of low-concentrated weak acids from descaling products.

Clin Toxicol (Phila) 2021 Jun 14:1-5. Epub 2021 Jun 14.

Dutch Poisons Information Center (DPIC), University Medical Center Utrecht, Utrecht, The Netherlands.

Introduction: The accidental ingestion of diluted household descaling products by infants is a phenomenon that poison control centers regularly encounter. Feeding infants with baby milk prepared with water from electric kettles still containing descaler is a common way of exposure. This study aimed to determine the risks related to ingestion of (diluted) descalers by infants. Read More

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Discovery and Characterization of Benzimidazole Derivative XY123 as a Potent, Selective, and Orally Available RORγ Inverse Agonist.

J Med Chem 2021 Jun 14. Epub 2021 Jun 14.

Guangdong Provincial Key Laboratory of Biocomputing, Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 510530, China.

Receptor-related orphan receptor γ (RORγ) has emerged as an attractive therapeutic target for the treatment of cancer and inflammatory diseases. Herein, we report our effort on the discovery, optimization, and evaluation of benzothiazole and benzimidazole derivatives as novel inverse agonists of RORγ. The representative compound (designated as XY123) potently inhibited the RORγ transcription activity with a half-maximal inhibitory concentration (IC) value of 64 nM and showed excellent selectivity against other nuclear receptors. Read More

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Worse capecitabine treatment outcome in patients with a low skeletal muscle mass is not explained by altered pharmacokinetics.

Cancer Med 2021 Jun 14. Epub 2021 Jun 14.

Department of Pharmacy & Pharmacology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

Background: A low skeletal muscle mass (SMM) has been associated with increased toxicity and shorter survival in cancer patients treated with capecitabine, an oral prodrug of 5-fluorouracil (5-FU). Capecitabine and its metabolites are highly water-soluble and, therefore, more likely to distribute to lean tissues. The pharmacokinetics (PK) in patients with a low SMM could be changed, for example, by reaching higher maximum plasma concentrations. Read More

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Validation of a Population Pharmacokinetic Model of Vortioxetine Using Therapeutic Drug Monitoring Data.

Clin Pharmacokinet 2021 Jun 14. Epub 2021 Jun 14.

Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway.

Introduction: Vortioxetine is an antidepressant primarily metabolized by the polymorphic enzyme cytochrome P450 (CYP) 2D6. A population pharmacokinetic (popPK) model of vortioxetine and its CYP2D6-dependent metabolite was recently published.

Objective: The aim of the current study was to assess the predictive performance of the popPK model using vortioxetine concentration measurements from a clinical setting. Read More

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Calycosin-loaded nanoliposomes as potential nanoplatforms for treatment of diabetic nephropathy through regulation of mitochondrial respiratory function.

J Nanobiotechnology 2021 Jun 13;19(1):178. Epub 2021 Jun 13.

Department of Nephrology, The First Hospital Affiliated To Jinan University, NO.613, Huangpu Avenue West, Guangzhou, 510150, China.

Backgrounds: One of the most common complications in diabetic nephropathy is generation of high levels of ROS which can be regulated by herbal antioxidants. However, polyphenols like calycosin, the bioactive compound of Radix astragali suffer from low solubility and poor bioavailability.

Methods: Therefore, in the present study, calycosin-loaded nanoliposomes were fabricated and characterized by TEM, DLS and FTIR techniques. Read More

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Comparison of Various Approaches to Translate Non-Linear Pharmacokinetics of Monoclonal Antibodies from Cynomolgus Monkey to Human.

Eur J Drug Metab Pharmacokinet 2021 Jun 13. Epub 2021 Jun 13.

Translation Bioscience, Human Health Therapeutics, National Research Council of Canada, Ottawa, ON, Canada.

Background And Objectives: The prediction of pharmacokinetics of monoclonal antibodies (mAbs) exhibiting non-linear pharmacokinetics in preclinical species to human is challenging, and very limited scientific work has been published in this field of research. Therefore, we have conducted an elaborate comparative assessment to determine the most reliable preclinical to clinical scaling strategy for mAbs with non-linear pharmacokinetics.

Methods: We have compared three different scaling approaches to predict human pharmacokinetics from cynomolgus monkey. Read More

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Evaluation of the Effect of Proton Pump Inhibitors on the Efficacy of Dacomitinib and Gefitinib in Patients with Advanced Non-Small Cell Lung Cancer and EGFR-Activating Mutations.

Oncol Ther 2021 Jun 13. Epub 2021 Jun 13.

Clinical Pharmacology, Pfizer Inc, 10555 Science Center Drive, CB10/002/2533, San Diego, CA, 92121, USA.

Introduction: Dacomitinib and gefitinib are irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) indicated for the first-line treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Pharmacokinetic (PK) studies in healthy volunteers suggested that acid-reducing drugs such as proton pump inhibitors (PPI) decreased dacomitinib and gefitinib exposure by limiting the pH-dependent absorption. This analysis retrospectively evaluates the effect of concomitant PPI use on dacomitinib exposure and on progression-free survival (PFS) and overall survival (OS) in patients treated with dacomitinib 45 mg QD or gefitinib 250 mg QD in a 1:1 randomized phase 3 study (ARCHER 1050). Read More

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A minimal physiologically based pharmacokinetic model for high-dose methotrexate.

Cancer Chemother Pharmacol 2021 Jun 13. Epub 2021 Jun 13.

PSE-Lab, Process Systems Engineering Laboratory, Dipartimento di Chimica, Materiali e Ingegneria Chimica "Giulio Natta", Politecnico di Milano, Piazza Leonardo da Vinci 32, 20133, Milano, Italy.

Purpose: High-dose methotrexate (HDMTX) is administered for the treatment of a variety of malignant tumors. Wide intra- and inter-individual variabilities characterize the pharmacokinetics of MTX, which is mostly excreted renally. HDMTX dosages are prescribed as a function of body surface area whereas dose adjustments depending on renal function are not well defined. Read More

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Model-informed precision dosing to optimise immunosuppressive therapy in renal transplantation.

Drug Discov Today 2021 Jun 10. Epub 2021 Jun 10.

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Leiden, the Netherlands; Leiden Network for Personalised Therapeutics, Leiden, the Netherlands. Electronic address:

Immunosuppressive therapy is pivotal for sustained allograft and patient survival after renal transplantation. However, optimally balanced immunosuppressive therapy is challenged by between-patient and within-patient pharmacokinetic (PK) variability. This could warrant the application of personalised dosing strategies to optimise individual patient outcomes. Read More

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Chitosan coated nanoparticles for efficient delivery of bevacizumab in the posterior ocular tissues via subconjunctival administration.

Carbohydr Polym 2021 Sep 18;267:118217. Epub 2021 May 18.

Department of Pharmaceutics, School of Pharmaceutical Education & Research, Jamia Hamdard, Hamdard Nagar, New Delhi, India.

In several ocular diseases, vascular endothelial growth factor (VEGF) level has been found to be unregulated. Bevacizumab, an anti-VEGF drug, is the most commonly used off level drug for diabetic retinopathy (DR). The present study was to evaluate the chitosan-coated poly (lactide-co-glycolic acid) nanoparticles (CS-PLGA NPs) for sustained and effective delivery of bevacizumab to posterior ocular tissues. Read More

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September 2021

Benzofuranyl-2-imidazoles as imidazoline I receptor ligands for Alzheimer's disease.

Eur J Med Chem 2021 May 20;222:113540. Epub 2021 May 20.

Laboratory of Medicinal Chemistry (Associated Unit to CSIC), Department of Pharmacology, Toxicology and Medicinal Chemistry, Faculty of Pharmacy and Food Sciences, Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, 27-31, E-08028, Barcelona, Spain. Electronic address:

Recent findings unveil the pharmacological modulation of imidazoline I receptors (I-IR) as a novel strategy to face unmet medical neurodegenerative diseases. In this work, we report the chemical characterization, three-dimensional quantitative structure-activity relationship (3D-QSAR) and ADMET in silico of a family of benzofuranyl-2-imidazoles that exhibit affinity against human brain I-IR and most of them have been predicted to be brain permeable. Acute treatment in mice with 2-(2-benzofuranyl)-2-imidazole, known as LSL60101 (garsevil), showed non-warning properties in the ADMET studies and an optimal pharmacokinetic profile. Read More

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Prediction of fluoxetine and norfluoxetine pharmacokinetic profiles using physiologically based pharmacokinetic modeling.

J Clin Pharmacol 2021 Jun 12. Epub 2021 Jun 12.

College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.

Fluoxetine is a selective serotonin reuptake inhibitor that is metabolized to norfluoxetine by CYP2D6, CYP2C19, and CYP3A4. A physiologically based pharmacokinetic (PBPK) model for fluoxetine and norfluoxetine metabolism was developed to predict and investigate changes in concentration-time profiles according to fluoxetine dosage in the Korean population. The model was developed based on the Certara repository model and information gleaned from the literature. Read More

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Mechanistic Computational Model for Extrapolating In vitro Thyroid Peroxidase (TPO) Inhibition Data to Predict Serum Thyroid Hormone Levels in Rats.

Toxicol Sci 2021 Jun 12. Epub 2021 Jun 12.

Center for Computational Toxicology and Exposure, Research Triangle Park, NC.

High throughput (HTP) in vitro assays are developed to screen chemicals for their potential to inhibit thyroid hormones (THs) synthesis. Some of these experiments, such as the thyroid peroxidase (TPO) inhibition assay, are based on thyroid microsomal extracts. However, the regulation of thyroid disruption chemicals (TDCs) is based on THs in vivo serum levels. Read More

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Population Pharmacokinetics of Oral Levofloxacin in Healthy Volunteers and Dosing Optimization for Multidrug-resistant Tuberculosis Therapy.

Biopharm Drug Dispos 2021 Jun 11. Epub 2021 Jun 11.

Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkla, 90110, Thailand.

Background: Levofloxacin is considered to be a key component of multidrug-resistant tuberculosis (MDR-TB) regimen. However, there is considerable concern regarding the subtherapeutic concentrations of currently used doses and the development of drug resistance.Therefore, this study aimed to describe the population pharmacokinetics of oral levofloxacin in healthy volunteers and to evaluate the probability of target attainment (PTA) in an attempt to optimize the dosing regimens for MDR-TB therapy. Read More

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Ayurveda botanicals in COVID-19 management: An in silico multi-target approach.

PLoS One 2021 11;16(6):e0248479. Epub 2021 Jun 11.

AYUSH-Center of Excellence, Center for Complementary and Integrative Health, Interdisciplinary School of Health Sciences, Savitribai Phule Pune University, Pune, India.

The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. Read More

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Kinetic disposition of diazepam and its metabolites after intravenous administration of diazepam in the horse: Relevance for doping control.

J Vet Pharmacol Ther 2021 Jun 11. Epub 2021 Jun 11.

Institute of Biochemistry, Center for Preventive Doping Research, German Sport University Cologne, Cologne, Germany.

In horses, the benzodiazepine diazepam (DIA) is used as sedative for pre-medication or as an anxiolytic to facilitate horse examinations. As the sedative effects can also be abused for doping purposes, DIA is prohibited in equine sports. DIA is extensively metabolized to several active metabolites such as nordazepam, temazepam and oxazepam (OXA). Read More

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Panobinostat penetrates the blood-brain barrier and achieves effective brain concentrations in a murine model.

Cancer Chemother Pharmacol 2021 Jun 11. Epub 2021 Jun 11.

Department of Clinical Pharmacy and Pharmacy Services, Inpatient Hematology, University of Michigan College of Pharmacy, 1540 E. Hospital Dr., CW 7-251B, Ann Arbor, MI, 48109-5008, US.

Purpose: Panobinostat, an orally bioavailable pan-HDAC inhibitor, has demonstrated potent activity in multiple malignancies, including pediatric brain tumors such as DIPG, with increased activity against H3K27M mutant cell lines. Given limited evidence regarding the CNS penetration of panobinostat, we sought to characterize its BBB penetration in a murine model.

Methods: Panobinostat 15 mg/kg was administered IV to 12 CD-1 female mice. Read More

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Pharmacokinetics of Five Alkaloids and their Metabolites in Normal and Diabetic Rats after Oral Administration of Rhizoma coptidis.

Planta Med 2021 Jun 10. Epub 2021 Jun 10.

School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Rhizoma coptidis has been clinically used for a long time for the treatment of various diseases in China, such as hypertension, diabetes, and inflammation. Previous studies have shown that alkaloid components of Rhizoma coptidis extract could be extensively metabolized and the metabolites were also considered to be the therapeutic material basis. However, until now, pharmacokinetic studies of the metabolites have not been revealed yet. Read More

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Pharmacokinetic studies of [ Ga]Ga-PSMA-11 in patients with biochemical recurrence of prostate cancer: detection, differences in temporal distribution and kinetic modelling by tissue type.

Eur J Nucl Med Mol Imaging 2021 Jun 10. Epub 2021 Jun 10.

Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69210, Heidelberg, Germany.

Purpose: [ Ga]Ga-PSMA-11 is a promising radiopharmaceutical for detecting tumour lesions in prostate cancer, but knowledge of the pharmacokinetics is limited. Dynamic PET-CT was performed to investigate the tumour detection and differences in temporal distribution, as well as in kinetic modelling of [ Ga]Ga-PSMA-11 by tissue type.

Methods: Dynamic PET-CT over the lower abdomen and static whole-body PET-CT 80-90 min p. Read More

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X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson's Disease.

J Med Chem 2021 Jun 10. Epub 2021 Jun 10.

Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) have been closely linked to the pathogenesis of Parkinson's disease (PD); nevertheless, development of dual hIDO1 and hTDO inhibitors to evaluate their potential efficacy against PD is still lacking. Here, we report biochemical, biophysical, and computational analyses revealing that 1-indazole-4-amines inhibit both hIDO1 and hTDO by a mechanism involving direct coordination with the heme ferrous and ferric states. Crystal structure-guided optimization led to , which manifested IC values of 0. Read More

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Population Pharmacokinetic And Exposure-Response Analyses Of Intravenous And Subcutaneous Rituximab In Patients With Chronic Lymphocytic Leukemia.

CPT Pharmacometrics Syst Pharmacol 2021 Jun 10. Epub 2021 Jun 10.

Roche Innovation Center Basel, Basel, Switzerland.

A subcutaneous formulation of the anti-CD20 antibody rituximab has been developed. Fixed-dose subcutaneous rituximab delivers non-inferior serum trough concentrations (C ), ensuring similar target saturation and comparable efficacy/safety to intravenous rituximab, but with simplified and shortened preparation and administration. We aimed to characterize the pharmacokinetic and exposure-response properties of subcutaneous rituximab. Read More

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Pharmacokinetics and pharmacodynamics of enrofloxacin treatment of Escherichia coli in a murine thigh infection modeling.

BMC Vet Res 2021 Jun 9;17(1):212. Epub 2021 Jun 9.

Department of Veterinary Surgery, College of Veterinary Medicine, Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin, 150030, China.

Background: Enrofloxacin is an antibacterial drug with broad-spectrum activity that is widely indicated for veterinary use. We aim to develop the clinical applications of Enrofloxacin against colibacillosis by using the neutropenic mice thigh infection model.

Results: The minimum inhibitory concentration (MIC) distribution of 67 isolated E. Read More

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Population pharmacokinetic and exploratory exposure-response analysis of the fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection in patients with HER2-positive early breast cancer in the FeDeriCa study.

Cancer Chemother Pharmacol 2021 Jun 9. Epub 2021 Jun 9.

Genentech, Inc., 1 DNA Way, South San Francisco, CA, 94080, USA.

Purpose: To characterize pertuzumab pharmacokinetics (PK) in FeDeriCa (NCT03493854: fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection [PH FDC SC] versus intravenous pertuzumab plus trastuzumab); derive individual pertuzumab exposures in the PH FDC SC arm for subsequent pertuzumab exposure-response (ER) analyses; compare observed trastuzumab PK with predicted exposures from a previous SC trastuzumab model; assess whether pertuzumab affects trastuzumab PK; evaluate pertuzumab exposure-efficacy and -safety relationships and support the approved SC dosing regimen.

Methods: Population pharmacokinetic modeling and simulations were used to describe the data. Standard goodness-of-fit diagnostics and prediction-corrected visual predictive checks were used for model performance assessment. Read More

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Biomimetic artificial cells to model the effect of membrane asymmetry on chemoresistance.

Chem Commun (Camb) 2021 Jun 9. Epub 2021 Jun 9.

University of Victoria, Department of Chemistry, Victoria BC, V8W 2Y2, Canada.

We present a microfluidic platform that enables the formation of bespoke asymmetric droplet interface bilayers (DIBs) as artificial cell models from naturally-derived lipids. We use them to perform pharmacokinetic assays to quantify how lipid asymmetry affects the permeability of the chemotherapy drug doxorubicin. Previous attempts to model bilayer asymmetry with DIBs have relied on the use of synthetic lipids to achieve asymmetry. Read More

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