Pharmacokinetic comparison of generic and trade formulations of lamivudine, stavudine and nevirapine in HIV-infected Malawian adults.
BACKGROUND
The Malawian antiretroviral program uses generic Triomune (stavudine, lamivudine, and nevirapine).


OBJECTIVE
To determine the pharmacokinetics and bioequivalence of generic and trade formulations of stavudine, lamivudine, and nevirapine in HIV-infected Malawians.


METHODS
This randomized, open label, cross-over study comprised of six men and six women currently receiving Triomune-40 TM who were randomized to the generic or trade formulation of stavudine (40 mg twice daily), lamivudine (150 mg twice daily) and nevirapine (200 mg twice daily). After at least 21 days, the alternate formulation was administered. At the end of each period, six blood samples were collected over 8 h. Bioequivalence was achieved if the 90% confidence interval (CI) for the geometric mean ratio (GMR) of generic:trade formulations for maximum plasma concentration (Cmax) and the area under the concentration-time curve (AUC) was within 0.8-1.25.


RESULTS
Mean patient age, weight, and height were 38.4 years (SD, 7.7), 71.2 kg (SD, 7.0), and 164.8 cm (SD, 6.3), respectively. The GMR for stavudine, lamivudine, and nevirapine were 1.4 (90% CI, 1.2-1.7), 1.1 (90% CI, 0.8-1.6), and 0.9 (90% CI, 0.7-1.2), respectively, for Cmax; and 1.1 (90% CI, 1.0 1.2), 1.0 (90% CI, 0.7-1.3), and 0.9 (90% CI, 0.7-1.1), respectively, for AUC0-8h. Regardless of formulation, Malawians had higher nevirapine exposures compared with historical reports of Western HIV-infected patients.


CONCLUSIONS
Although exposures were similar, Triomune did not meet the strict definition of bioequivalence for these drugs. Patients taking Triomune had notably higher stavudine Cmax values. Antiretroviral pharmacokinetics and bioequivalence of generic formulations should be evaluated in the populations in which they are being used.
Hosseinipour
Mina C
MC
University of North Carolina Project, Lilongwe Malawi.
Corbett
Amanda H
AH
Kanyama
Cecelia
C
Mshali
Idah
I
Phakati
Severiano
S
Rezk
Nazer L
NL
van der Horst
Charles
C
Kashuba
Angela D M
AD
D000328:Adult; D019380:Anti-HIV Agents / Q000493:pharmacokinetics*; D023241:Antiretroviral Therapy, Highly Active; D019540:Area Under Curve; D018791:CD4 Lymphocyte Count; D016001:Confidence Intervals; D018592:Cross-Over Studies; D004334:Drug Administration Schedule; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D019259:Lamivudine / Q000493:pharmacokinetics*; D008295:Malawi; D008297:Male; D019829:Nevirapine / Q000493:pharmacokinetics*; D018119:Stavudine / Q000493:pharmacokinetics*; D013810:Therapeutic Equivalency; D019562:Viral Load
D019380:Anti-HIV Agents; D016568:Drugs, Generic; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine