European journal of drug metabolism and pharmacokinetics
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Eur J Drug Metab Pharmacokinet · Mar 2021
Clinical TrialPharmacokinetics of Morphine and Morphine-6-Glucuronide During Postoperative Pain Therapy in Cardiac Surgery Patients.
Morphine is a standard analgesic drug for postoperative pain therapy. This study aimed to evaluate the pharmacokinetics of morphine and its active metabolite morphine-6-glucuronide (M6G) in cardiac surgery patients during postoperative analgesia. ⋯ The pharmacokinetics of morphine and M6G in pain therapy of cardiac surgery patients could be well described by standard compartmental models. Cardiac output was identified as a significant covariate for morphine clearance, whereas renal function was identified as the most significant covariate for clearance of M6G. These effects should be particularly considered if morphine is administered as a continuous infusion. The developed pharmacokinetic model also enables patient-controlled target-controlled infusion for pain therapy with morphine.
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Eur J Drug Metab Pharmacokinet · Dec 2020
Pharmacokinetic Basis of the Hydroxychloroquine Response in COVID-19: Implications for Therapy and Prevention.
Chloroquine/hydroxychloroquine has recently been the subject of intense debate regarding its potential antiviral activity against SARS-Cov-2, the etiologic agent of COVID-19. Some report possible curative effects; others do not. Therefore, the objective of this study was to simulate possible scenarios of response to hydroxychloroquine in COVID-19 patients using mathematical modeling. ⋯ These considerations may not only be applied to chloroquine/hydroxychloroquine but may have more general implications for development of anti-COVID-19 combination therapies and prevention strategies through an increased death rate of the infected cells.
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Eur J Drug Metab Pharmacokinet · Aug 2020
A Population Pharmacokinetics Model for Vancomycin Dosage Optimization Based on Serum Cystatin C.
Renal function has an important influence on the pharmacokinetics of vancomycin, and serum cystatin C (CysC) exhibits accurate predictive performance as a marker for renal function. This study aimed to develop a population pharmacokinetics (PopPK) model of vancomycin based on serum CysC in pediatric patients. In addition, vancomycin dosage was optimized with the area under the serum concentration-time curve over 24 h (AUC0-24)/minimum inhibitory concentration (MIC) ratio in the target range of 400-700 and the steady-state trough concentration (Css,trough). ⋯ The pharmacokinetic parameters for vancomycin in pediatric patients were estimated using a serum CysC model. The simulated dosages provide a reference for vancomycin therapy.
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Eur J Drug Metab Pharmacokinet · Feb 2020
Randomized Controlled TrialEffect of Fluconazole and Itraconazole on the Pharmacokinetics of Erdafitinib in Healthy Adults: A Randomized, Open-Label, Drug-Drug Interaction Study.
Erdafitinib, an oral selective pan-fibroblast growth factor receptor (FGFR) kinase inhibitor, is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4. The aim of this phase 1 study was to assess the pharmacokinetics and safety of erdafitinib in healthy participants when coadministered with fluconazole (moderate CYP2C9 and CYP3A inhibitor), and itraconazole (a strong CYP3A4 and P-glycoprotein inhibitor). The effect of CYP2C9 genotype variants (*1/*1, *1/*2, *1/*3) on the pharmacokinetics of erdafitinib was also investigated. ⋯ Coadministration of fluconazole or itraconazole or other moderate/strong CYP2C9 or CYP3A4 inhibitors may increase exposure to erdafitinib in healthy adults and thus may warrant erdafitinib dose reduction or use of alternative concomitant medications with no or minimal CYP2C9 or CYP3A4 inhibition potential.
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Eur J Drug Metab Pharmacokinet · Dec 2018
Comparative StudyEvaluation of FOCEI and SAEM Estimation Methods in Population Pharmacokinetic Analysis Using NONMEM® Across Rich, Medium, and Sparse Sampling Data.
First-order conditional estimation with interaction (FOCEI) is one of the most commonly used estimation methods in nonlinear mixed effects modeling, while the stochastic approximation expectation maximization (SAEM) is the newer estimation algorithm. This work aimed to compare the performance of FOCEI and SAEM methods when using NONMEM® with the classical one- and two-compartment models across rich, medium, and sparse data. ⋯ For the classical one- and two-compartment models, FOCEI method exhibited comparable performance similar to SAEM method but with significantly shorter runtimes across rich, medium, and sparse sampling scenarios.