Antiandrogen pretreatment alters cocaine pharmacokinetics in men.

Among cocaine users, men experience more adverse brain and vascular effects than their female counterparts. This could be caused by testosterone, which may potentiate some of cocaine's effects. We examined whether antiandrogen (flutamide, FL) pretreatment alters cocaine's acute behavioral, physiologic, and pharmacokinetic effects in men with histories of occasional cocaine use. Participants (N = 8) were pretreated with oral FL (250 mg) and placebo on separate study days followed by intravenous (IV) cocaine (0.4 mg/kg). Vital signs, subjective ratings, and blood samples for cocaine and metabolites were obtained at baseline and for 90 minutes after cocaine administration. FL, itself, had no effects on physiologic or subjective responses; however, after cocaine, heart rate recovered faster with FL pretreatment. Flutamide reduced peak plasma cocaine levels (Wilcoxon signed-rank z = 2.1, P < 0.04) and area under the curve (AUC; z = 1.96, P < 0.05). Additionally, FL reduced EME levels (z = 1.96, P < 0.05) and AUC for BE and EME (z = 2.38, P < 0.02 and z = 1.96, P < 0.05, respectively). These results suggest that FL may alter cocaine pharmacokinetics in men. Because cocaine and BE are vasoconstrictive, the data imply that FL might reduce some of cocaine's cardiovascular effects.