Journal
JOURNAL OF CLINICAL PHARMACOLOGY
Volume 49, Issue 9, Pages 1079-1090Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/0091270009338482
Keywords
NRTIs; pharmacokinetics; UGT2B7; rifampin; interindividual variability
Categories
Funding
- Lifespan/Tufts/Brown Center [P30AI042853]
- NIH K23 developmental award [NIH K23 AI071760]
- University of North Carolina at Chapel Hill [AI50410]
- National Institute of General Medical Sciences (NIGMS), National Institutes of Health (Bethesda, Maryland) [R01GM061834]
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available