Please use this identifier to cite or link to this item: http://cmuir.cmu.ac.th/jspui/handle/6653943832/70818
Title: Dosage Optimization of Efavirenz Based on a Population Pharmacokinetic–Pharmacogenetic Model of HIV-infected Patients in Thailand
Authors: Piyawat Chaivichacharn
Anchalee Avihingsanon
Weerawat Manosuthi
Sasiwimol Ubolyam
Siraprapa Tongkobpetch
Vorasuk Shotelersuk
Baralee Punyawudho
Keywords: Medicine
Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Jul-2020
Abstract: © 2020 Elsevier Inc. Purpose: Efavirenz exhibits high interindividual variability in plasma concentrations, leading to unpredictable efficacy and toxicity. Polymorphism of CYP2B6 516G > T has been found to predominantly contribute to efavirenz variability. However, dosage recommendations incorporating CYP2B6 516G > T polymorphism have not been investigated in the Thai population. This study aimed to develop a population model of the pharmacokinetic properties of efavirenz, and to investigate the impact of patients' characteristics and CYP2B6 516G > T polymorphism on the pharmacokinetic properties of efavirenz. Model-based simulations were performed to provide genotype-based dosage optimization in a Thai population. Methods: Plasma efavirenz concentrations measured at 12 h post-dose in 360 Thai HIV-infected patients with and without tuberculosis were analyzed by the nonlinear mixed-effects modeling approach. A 1-compartment model with first-order absorption and elimination was used for describing the pharmacokinetic properties of efavirenz. Findings: The allele frequency of CYP2B6 516G > T was 34.17%. The efavirenz oral clearance were 11.9, 8.0, and 2.8 L/h in patients weighing 57 kg and having the CYP2B6 516 GG, 516 GT, and 516 TT genotypes, respectively. The use of rifampicin increased efavirenz oral clearance by 28%. The results from the simulations suggest that efavirenz dosages of 400, 300, and 100 mg once daily in Thai HIV mono-infected patients, and 800, 600, and 200 mg once daily in HIV/tuberculosis co-infected patients carrying CYP2B6 516 GG, 516 GT, and 516 TT, respectively. Implication: The results from this study provide a rationale for efavirenz dose adjustment based on CYP2B6 516G > T polymorphism in Thai HIV-infected patients, which could help to improve treatment outcomes in this population. ClinicalTrials.gov identifier: NCT01138267.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85085047562&origin=inward
http://cmuir.cmu.ac.th/jspui/handle/6653943832/70818
ISSN: 1879114X
01492918
Appears in Collections:CMUL: Journal Articles

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