| Abstract |
The prevalence of HIV infection among older people and women is increasing. Age and gender has been shown to have an effect on the pharmacokinetics of many cytochrome P450 substrates in clinical pharmacokinetic (PK) studies. In addition, the antiretroviral therapy in older people can be complicated by the co-morbidities and co-administered medications. The PK of antiretroviral agents may be altered due to age-related decline in hepatic and/or renal clearance. However, there is very little prospective data on the effect of age and gender on the PK of ARV agents. Specifically, the effect of age and gender on the PK of efavirenz, one of the most commonly used antiretroviral agent has, only been studied retrospectively, but never prospectively. We proposed to evaluate the effect of age and gender on the clearance of efavirenz in a prospective, open label, PK study of a single oral dose (600mg) in HIV-uninfected healthy 'young' (18-45) years and 'older' (>65 years) men and women (Total N=48, 12 in each of four group). The specific aims of the proposal are: To determine the effect of age and gender on the clearance of EFV in HIV-uninfected healthy 'young' and 'older' men and women. We hypothesize that the clearance of efavirenz will decrease (and therefore, the area under the curve will increase) with age, and that it will differ between men and women due to gender-related differences. The effect of genetics (polymorphism of CYP2B6) on the clearance of EFV will be adjusted for. These data will further our understanding of the host factors underlying the inter-individual differences in the PK of ARV agents. The proposal can contribute to the clinical care of HIV infection in older people and women by providing a prospective, intensive PK data that will determine the effect of age and gender on the PK of ARV agents. This proposal represents collaboration between established investigators working in HIV clinical research (Dr. Wanke) and clinical pharmacology (Dr. Greenblatt), both of whom will mentor Dr. Rhee. This proposal will provide preliminary data for a K23 submission by Dr. Rhee focusing on the difference in PK of ARV agents in older HIV-infected people.
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