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This Article Full Text Full Text (PDF) All Versions of this Article: 0091270009338482v1 49/9/1079    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Request Reprints Google Scholar Articles by Kwara, A. Articles by Court, M. H. PubMed PubMed Citation Articles by Kwara, A. Articles by Court, M. H. Social Bookmarking                         What's this?

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

From the Warren Alpert Medical School of Brown University, Providence, Rhode Island (Dr Kwara); University of Ghana Medical School, Accra, Ghana (Dr Lartey, Mr Boamah); University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (Dr Rezk, Dr Kashuba); Korle-Bu Teaching Hospital, Accra, Ghana (Dr Oliver-Commey, Dr Kenu); and Tufts University School of Medicine, Boston, Massachusetts (Dr Court).

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.

Key Words: NRTIs • pharmacokinetics • UGT2B7 • rifampin • interindividual variability

Address for reprints: Awewura Kwara, MD, The Miriam Hospital, 164 Summit Avenue, Providence, RI 02906; e-mail: akwara{at}lifespan.org.

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