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

Abstract

Limited data are available on antiretroviral drug concentrations in seminal plasma during a dosing interval. Further, since human ejaculate is composed of fluids originating from the testes, the seminal vesicles, and the prostate, all having different physiological characteristics, drug concentrations in total seminal plasma do not necessarily reflect concentrations in the separate compartments. Five human immunodeficiency virus type 1-infected patients 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 ejaculate technique to separate seminal plasma in two fractions, representing fluids from the testes and prostate (first fraction) and fluids from the seminal 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 sexual abstinence. NVP and IDV showed time-dependent concentrations in seminal plasma, with peak concentrations in both fractions at 2 and 2 to 5 h, respectively, after drug ingestion. The NVP concentrations were not significantly different between the first and second fractions of the ejaculate at all time points measured and were in the therapeutic range, except for the predose concentration in two patients. The median (range) predose IDV concentrations 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 conclusion, NVP and IDV concentrations in seminal plasma are dependent on the time after drug ingestion. Furthermore, our data suggest that NVP and IDV achieve therapeutic concentrations in both the testes and prostate and the seminal vesicles throughout the dosing interval.

Figures

FIG. 1

Fructose and spermatozoa concentrations in split ejaculate samples at 0, 2, 5, or 8 h after drug ingestion. The left circle of each line represents the fructose or spermatozoa concentration in the first ejaculate fraction; the right circle represents the fructose or spermatozoa concentration in the second ejaculate fraction.

FIG. 2

(A) NVP concentrations in blood plasma and seminal plasma during the dosing interval. All patients used NVP at 200 mg b.i.d. Open triangles, NVP concentration in the first ejaculate fraction; black circles, NVP concentration in the second ejaculate fraction; asterisks, NVP concentration in a random blood plasma sample; solid thin line, median NVP concentrations measured in a reference population of HIV-1-infected patients using NVP at 200 mg b.i.d., with interquartile ranges represented as dotted lines (19); MEC, minimal effective concentration of NVP in blood plasma (3.4 μg/ml) (9, 21). The lower limits of quantification of NVP in blood plasma and seminal plasma were 50 and 100 ng/ml, respectively (17). (B) IDV concentrations in blood plasma and seminal plasma during the dosing interval. All patients used IDV (800 mg b.i.d.) and RTV (100 mg b.i.d.), except for patient 014, who used IDV (1,000 mg b.i.d.) and RTV (100 mg b.i.d.). Open triangles, IDV concentration in the first ejaculate fraction; black circles, IDV concentration in the second ejaculate fraction; asterisks, IDV concentration in a random blood plasma sample; solid thin line, median IDV concentrations measured in a reference population of HIV-1-infected patients using IDV (800 mg b.i.d.) plus RTV (100 mg b.i.d.), with the interquartile ranges represented as dotted lines (18); MEC, minimal effective concentration of IDV in blood plasma (100 ng/ml) (3). The lower limits of quantification of IDV in blood plasma and seminal plasma were 25 and 50 ng/ml, respectively (16).