Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
High prevalence of the CYP2B6 516G→T(*6) variant and effect on the population pharmacokinetics of efavirenz in HIV/AIDS outpatients in Zimbabwe
European Journal of Clinical Pharmacology, Volume 64, No. 4, Year 2008
Notification
URL copied to clipboard!
Description
Objective: The study sought to investigate the relationship between efavirenz exposure and the CYP2B6 516G→T(*6) genotype in HIV/AIDS outpatients, using pharmacokinetic modelling and simulation. Methods: Blood samples where obtained from 74 outpatients treated with a combination regimen including 600 mg efavirenz daily for a duration of at least 3 weeks at clinics in Harare, Zimbabwe. The subjects were genotyped for the major CYP2B6 variant, CYP2B6*6, associated with reduced enzyme activity, using a PCR-RFLP method. Efavirenz plasma concentrations were determined by HPLC-UV. Population pharmacokinetic modelling and simulation of the data were performed in NONMEM VI. Results: A high allele frequency of the CYP2B6*6 allele of 49% was observed. Efavirenz plasma concentrations were above 4 mg/L in 50% of the patients. Genotype and sex were identified as predictive covariates of efavirenz disposition. Pharmacokinetic parameter estimates indicate that a dose reduction to 400 mg efavirenz per day is possible in patients homozygous for the CYP2B6*6 genotype without compromising therapeutic efficacy. Conclusion: The CYP2B6*6 allele occurs at a high frequency in people of African origin and is associated with high efavirenz concentrations. Simulations indicate that an a priori 35% dose reduction in homozygous CYP2B6*6 patients would maintain drug exposure within the therapeutic range in this group of patients. Our preliminary results suggest the conduct of a prospective clinical dose optimization study to evaluate the utility of genotype-driven dose adjustment in this population. © 2007 Springer-Verlag.
Authors & Co-Authors
Nyakutira, Christopher
Zimbabwe, Harare
African Institute of Biomedical Science and Technology
Zimbabwe, Harare
University of Zimbabwe
Röshammar, Daniel
Sweden, Gothenburg
Sahlgrenska Akademin
Chigutsa, Emmanuel
Zimbabwe, Harare
African Institute of Biomedical Science and Technology
Zimbabwe, Harare
University of Zimbabwe
Chonzi, Prosper
Zimbabwe, Harare
Harare City Health
Ashton, Michael
Sweden, Gothenburg
Sahlgrenska Akademin
Nhachi, Charles Fungai Brian
Zimbabwe, Harare
University of Zimbabwe
Masimirembwa, Collen Mutowembwa
Zimbabwe, Harare
African Institute of Biomedical Science and Technology
Statistics
Citations: 218
Authors: 7
Affiliations: 4
Identifiers
Doi:
10.1007/s00228-007-0412-3
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study
Study Locations
Zimbabwe