indinavir-sulfate and Erectile-Dysfunction

Topics: Abdominal Abscess; Acquired Immunodeficiency Syndrome; Adult; Aged; AIDS-Associated Nephropathy; Erectile Dysfunction; Humans; Indinavir; Kidney; Kidney Calculi; Lymphoma; Male; Male Urogenital Diseases; Middle Aged; Prostatic Diseases; Prostatitis; Sarcoma, Kaposi; Testicular Diseases; Urination Disorders

The objective of this study was to investigate if sildenafil influences the pharmacokinetics of nelfinavir. Five HIV-infected patients on steady-state nelfinavir-containing therapy were subject to pharmacokinetic sampling for nelfinavir concentration twice: without sildenafil and with sildenafil 25 mg as a single dose. There were no differences in the AUC, T(max), or C(max) of nelfinavir. In a similar design, two patients on indinavir and two patients on ritonavir combined with saquinavir were studied. In accordance with the literature, neither of these two treatments was affected. It is concluded that nelfinavir pharmacokinetics were unaffected by concomitant intake of a single dose of sildenafil.

Topics: Adult; Area Under Curve; Chromatography, High Pressure Liquid; Drug Interactions; Drug Therapy, Combination; Erectile Dysfunction; Half-Life; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Middle Aged; Nelfinavir; Piperazines; Purines; Ritonavir; Saquinavir; Sildenafil Citrate; Sulfones; Vasodilator Agents

A high proportion of individuals receiving highly active antiretroviral treatment (HAART) complain of sexual dysfunction (SD), encompassing a lack of desire or erectile dysfunction.. To determine whether SD was associated with particular components of the HAART regimens and to identify risk factors for the development of SD in patients on HAART.. A survey among patients with HIV infection using an anonymous questionnaire was conducted in 10 European countries between December 1998 and December 1999. A total of 904 individuals currently receiving antiretroviral agents were included in the analyses.. A decrease in sexual interest was significantly more frequently reported by subjects (men and women) using HAART containing protease inhibitors (PI) (308/766, 40%), compared with PI-naive patients (22/138, 16%; OR 3.55; 95% CI 2.15--5.89). In addition, a significantly larger number of PI-experienced men reported a decrease in sexual potency (216/628, 34%) compared with PI-naive men (12/99, 12%; OR 2.56; 95% CI 1.33--5.03). In multivariate analyses the following factors were associated with a decrease in sexual interest: a current PI-containing regimen, a history of a PI regimen, symptomatic HIV infection, age and homosexual contact as HIV transmission mode. Factors associated with a decrease in sexual potency were: current use of a PI-containing regimen, symptomatic HIV disease, age and the use of tranquillisers.. SD appears to be a common side-effect of HAART regimens containing a PI. The potential association between SD and other side-effects of HAART, such as lipodystrophy syndrome and neuropathy, should be investigated further.

Topics: Adult; Antiretroviral Therapy, Highly Active; Erectile Dysfunction; Female; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Male; Multivariate Analysis; Nelfinavir; Prevalence; Risk Factors; Ritonavir; Sexual Dysfunctions, Psychological; Surveys and Questionnaires

To determine whether treatment with protease inhibitors (PIs) is associated with male sexual dysfunction, we conducted a retrospective, cohort study of 254 adult male PI recipients who received care from the staff-model division of a large managed care organization in New England between 1993 and 1998. After a median of 5.0 years of observation, 80 incident cases of sexual dysfunction were observed. Relative to unexposed individuals, the rate of sexual dysfunction adjusted for confounding was most elevated with use of ritonavir (hazard ratio [HR], 2.83; 95% confidence interval [CI], 1.34-5.97; p =.006) followed by indinavir (HR, 1.69; 95% CI, 0.84-3.37; p =.14), nelfinavir (HR, 1.53; 95% CI, 0.66-3.54; p =.32) and saquinavir (HR, 1.25; 95% CI, 0.53-2.96; p =.60). We conclude that PIs, especially ritonavir, appear to increase the risk of sexual dysfunction.

Topics: Adolescent; Adult; Aged; Cohort Studies; Erectile Dysfunction; HIV Infections; HIV Protease Inhibitors; HIV-1; Humans; Indinavir; Male; Managed Care Programs; Middle Aged; Nelfinavir; New England; Retrospective Studies; Ritonavir; Saquinavir

Topics: Adolescent; Adult; Erectile Dysfunction; HIV Infections; HIV Protease Inhibitors; Hormones; Humans; Indinavir; Male; Middle Aged; Penile Erection; Peripheral Nervous System; Predictive Value of Tests; Reverse Transcriptase Inhibitors; Surveys and Questionnaires

The prevalence of erectile dysfunction in HIV-infected men is estimated to be 33%. Sildenafil citrate (Viagra; Pfizer Ltd, Sandwich, Kent, UK) is the first oral drug for this condition. Since sildenafil and the protease inhibitors are both metabolized by, and act as inhibitors of cytochrome P450 3A4, we evaluated the pharmacokinetics of the combination sildenafil plus indinavir in HIV-infected patients.. Six patients at steady state in treatment with indinavir participated in the study. On the first day blood samples for indinavir assay were drawn at times 0, 1, 2, 3, 4, 6 and 8 h after dosing. On the second study day patients received a single dose of 25 mg of sildenafil in addition to their routine morning medication. Blood samples were taken as described. Separated plasma was stored at -80 degrees C until analysis by high performance liquid chromatography. In a parallel study, the effect of indinavir, ritonavir, saquinavir and nelfinavir on the in vitro hepatic metabolism of sildenafil was assessed.. The geometric mean area under the concentration curve for 0-8 h (AUC0-8h) and maximum plasma concentration (Cmax) for indinavir were 19.69 microg/ml h (range, 9.19-31.99 microg/ml h) and 7.02 microg/ml (range, 2.33-16.17 microg/ml), respectively, on the first study day. In the presence of sildenafil, the mean AUC0-8h and Cmax of indinavir were 22.37 microg/ml h [range, 10.08-37.25 microg/ml h; 95% confidence interval (CI) for difference between means, -15 to 13.25) and 9.11 microg/ml (range, 3.41-22.78 microg/ml; 95% CI, -13 to 6.37), respectively. The geometric mean AUC0-8h and Cmax for sildenafil were 1631 ng/ml h (range, 643-2970 ng/ml h) and 384 ng/ml (range, 209-766 ng/ml) respectively. The AUC for sildenafil was 4.4 times higher than data from historical controls given either 50 mg or 100 mg of sildenafil and dose normalized to 25 mg. Indinavir was a potent inhibitor of sildenafil hepatic metabolism in vitro [concentration producing 50% inhibition of control enzyme activity (IC50) = 0.39 +/- 0.17 microM, mean +/- SD].. Co-administration of sildenafil 25 mg did not significantly alter the plasma indinavir levels. However, plasma sildenafil AUC was markedly increased in the presence of indinavir compared with historical controls. From the in vitro data, the mechanism of increase is indinavir inhibition of the hepatic metabolism of sildenafil. The magnitude of this interaction suggests a lower starting dose of sildenafil may be more appropriate in this clinical setting.

Topics: Adult; Drug Interactions; Erectile Dysfunction; HIV Infections; HIV Protease Inhibitors; Humans; Indinavir; Liver; Male; Middle Aged; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Sulfones