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• W2105822011 abstract "Emerging evidence suggests that female sex may be associated with increased risk of developing antiretroviral toxicities. Although the mechanisms of sex-related antiretroviral pharmacodynamic differences remain poorly understood and may be multifactorial, they appear to be mediated through a common pathway of pharmacokinetic variability between the sexes.This article reviews sex differences in the pharmacokinetics of the major classes of antiretroviral drugs currently approved for HIV treatment by the US Food and Drug Administration, identifies knowledge gaps, and provides recommendations for future research directions.To identify pertinent articles for this review, the MEDLINE database was searched from 1990 to June 2006 using the terms sex, gender, antiretroviral therapy, ART, HAART, pharmacokinetics, pharmacodynamics, NRTI, NNRTI, and protease inhibitors. Search results were restricted to English language and human studies. The reference lists of identified articles were also used, as well as abstracts from relevant conferences. In addition, individual antiretroviral drugs were searched by sex/gender or by pharmacokinetics.Current evidence, though limited, does suggest the existence of a sex disparity in antiretroviral pharmacokinetics, and such disparity has been shown to have pharmacodynamic implications for some drugs. Sex-mediated intracellular pharmaco-enhancement was associated with superior antiviral activities for the zidovudine and lamivudine members of the nucleoside reverse transcriptase inhibitor class. There appears to be divergent opinions about whether sex is a significant determinant of either nevirapine or efavirenz plasma concentrations. For certain protease inhibitors (PIs) (eg, saquinavir [SQV] and indinavir [IDV]), clinically significant relationships between sex differences in plasma drug concentrations and clinical outcomes have been observed. There appears to be a trend toward higher drug exposure in women than in men when PIs are boosted with ritonavir (RTV). Nelfinavir, the only PI that is currently administered unboosted with RTV, does not exhibit a sex difference in its plasma concentrations. Unboosted amprenavir exposure was lower in women compared with men. Sex differences in the pharmacokinetics of SQV and IDV were observed only in the setting of RTV boosting.A common weakness in many studies addressing sex-based differences in the pharmacokinetics of antiretroviral drugs is the relatively small number of women participating. Many of these studies were retrospective in design, and some had limited pharmacokinetic parameters for comparison. Antiretroviral treatment trials should be designed with sufficient power (adequate female participation) to detect sex-based differences both in pharmacokinetics and in clinical response. Future studies should explore the molecular basis for sex-based differences in plasma drug concentrations and antiretroviral drug response. The roles of drug transporter proteins and cellular kinases, and the activities of metabolizing enzymes in mediating differential plasma and intracellular antiretroviral concentrations, should be further assessed." @default.
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• W2105822011 date "2007-06-01" @default.
• W2105822011 modified "2023-10-18" @default.
• W2105822011 title "Antiretroviral pharmacokinetic profile: A review of sex differences" @default.
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• W2105822011 doi "https://doi.org/10.1016/s1550-8579(07)80025-8" @default.
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