11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retrovir Opportunistic Infect 2004 Feb 8-11; 11:(abstract no. 604)

Hitti J, Rosenkranz S, Cohn S, Kamemoto L, Kashuba A, Caten E, Aweeka F; Univ. of Washington, Seattle, USA

BACKGROUND: Recent data suggest that women may have decreased clearance of saquinavir compared to men. Our objective was to examine sex-specific systemic exposures for other selected antiretroviral medications and to determine whether any observed sex differences could be explained by weight.

METHODS: We conducted a retrospective analysis of the pharmacokinetics of efavirenz, indinavir and nelfinavir and its metabolite M8 in women and men from 6 AIDS Clinical Trials Group studies with intensive sampling (>/=5 data points). Data were available from 15 women and 82 men on efavirenz (600 mg once daily), 14 women and 63 men on indinavir (dose-normalized to 1200 mg twice daily) and 20 women and 133 men on nelfinavir (1250 mg twice daily). Subjects were on stable antiretroviral therapy for >/=7 days. Area under the concentration-time curve (AUC, ng*h/mL) was calculated from 0 to 24 hours for efavirenz, from 0 to 12 hours for indinavir, and from 0 to 6 hours for nelfinavir and M8 (for a truncated AUC). T-tests, ANOVA and regression models were used to test the univariate effects of sex, co-administered antiretroviral medications, weight and body mass index on log-transformed AUC. The final analysis of covariance models included sex and weight but not their interaction, and were used to predict the AUCs for women and men at an average weight of 70 kg and an 94th percentile weight of 100 kg.

RESULTS: Women had significantly lower efavirenz AUC compared with men, even after adjustment for weight (p <0.05). There were no significant sex differences in the AUC of indinavir, nelfinavir, or M8. Increased weight was significantly associated with lower efavirenz and indinavir AUC (p <0.05). The presence or absence of co-administered antiretroviral medications did not modify these observed associations. [table: see text]

CONCLUSIONS: Female sex was associated with lower efavirenz AUC regardless of weight. Greater weight was associated with lower AUC for efavirenz and indinavir in both sexes. These data suggest differences in the absorption or elimination of efavirenz between men and women. Further evaluations of exposure-efficacy/toxicity relationships are warranted with these medications.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.