Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation

Awewura Kwara, Margaret Lartey, Isaac Boamah, Naser L. Rezk, Joseph Oliver-Commey, Ernest Kenu, Angela D.M. Kashuba, Michael H. Court

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

There are limited data on the pharmacokinetics of generic nucleoside reverse transcriptase inhibitors (NRTIs) in native African populations, in whom they are commonly used. The authors characterized the pharmacokinetics of lamivudine (n = 27), zidovudine (n = 16), and stavudine (n = 11) in human immunodeficiency virus (HIV)/ tuberculosis (TB)-coinfected Ghanaians and evaluated associations between zidovudine metabolism and UDP- glucuronosyltransferase (UGT) 2B7 polymorphisms. Lamivudine, zidovudine, and stavudine apparent oral clearance (CL/F) values (mean ± SD [% coefficient of variation [CV]) were 7.3 ± 2.8 (39%), 31.9 ± 33.6 (106%), and 16.4 ± 5.8 (35%) mL/min/kg, respectively, whereas half-life values were 4.2 ± 1.9 (46%), 8.1 ± 7.9 (98%), and 1.5 ± 1.0 (65%) hours, respectively. Zidovudine CL/F was 196% higher (P =.004) in UGT2B7*1c (c.735A>G) carriers versus noncarriers. This was confirmed using human liver bank samples (n = 52), which showed 48% higher (P =.020) zidovudine glucuronidation and 33% higher (P =.015) UGT2B7 protein in UGT2B7*1c carriers versus noncarriers. In conclusion, generic NRTI pharmacokinetics in HIV/TB-coinfected Ghanaians are similar to other populations, whereas the UGT2B7*1c polymorphism may explain in part relatively high interindividual variability in zidovudine clearance.

Original languageEnglish
Pages (from-to)1079-1090
Number of pages12
JournalJournal of Clinical Pharmacology
Volume49
Issue number9
DOIs
Publication statusPublished - Sep 2009
Externally publishedYes

Keywords

  • Interindividual variability
  • NRTIs
  • Pharmacokinetics
  • Rifampin
  • UGT2B7

Fingerprint

Dive into the research topics of 'Interindividual variability in pharmacokinetics of generic nucleoside reverse transcriptase inhibitors in TB/HIV-coinfected ghanaian patients: UGT2B7*1c is associated with faster zidovudine clearance and glucuronidation'. Together they form a unique fingerprint.

Cite this