Pharmacokinetic profiles of nevirapine and indinavir in various fractions of seminal plasma

Limited data are available on antiretroviral drug concentrations in seminal plasma during a dosing interval. Further, since human ejaculate is compose d of fluids originating from the testes, the seminal vesicles, and the pros tate, all having different physiological characteristics, drug concentratio ns in total seminal plasma do not necessarily reflect concentrations in the separate compartments. Five human immunodeficiency virus type 1-infected p atients on nevirapine (NVP; 200 mg twice a day [b.i.d.]) and/or indinavir ( IDV; 800 mg b.i.d. with ritonavir, 100 mg b.i.d.) regimens used a split eja culate technique to separate seminal plasma in two fractions, representing fluids from the testes and prostate (first fraction) and fluids from the se minal vesicles (second fraction). Split-ejaculate samples were provided at 0, 2, 5, and 8 h after drug ingestion, on separate days after 3 days of sex ual abstinence. NVP and IDV showed time-dependent concentrations in seminal plasma, with peak concentrations in both fractions at 2 and 2 to 5 h, resp ectively, after drug ingestion. The NVP concentrations were not significant ly different between the first and second fractions of the ejaculate at all time points measured and were in the therapeutic range, except for the pre dose concentration in two patients. The median (range) predose IDV concentr ations in the first and second fractions of the ejaculate were 448 (353 to 1,015) ng/ml and 527 (240 to 849) ng/ml, respectively (P = 0.7). In conclus ion, NVP and IDV concentrations in seminal plasma are dependent on the time after drug ingestion. Furthermore, our data suggest that NVP and IDV achie ve therapeutic concentrations in both the testes and prostate and the semin al vesicles throughout the dosing interval.