Faster clearance of sustained release verapamil in men versus women: Continuing observations on sex-specific differences after oral administration ofverapamil

Pharmacokinetic studies after administration of 120 mg oral sustained- and regular-release racemic verapamil were performed in 13 healthy subjects (se ven men, age 74 +/- 4 years [mean +/- SD], weight 69.9 +/- 5.4 kg, and body mass index 24.6 +/- 2.2]; and six women, age 65 +/- 13 years, weight: 65 /- 9.9 kg, and body mass index 25.3 +/- 3). Verapamil was measured by HPLC, concentration versus time data analyzed by noncompartmental models, and st atistical analyses performed by ANOVA for repeated measurements. The area u nder the concentration versus time curve (AUC) after administration of sust ained-release verapamil was 48,951 +/- 18,079 ng/mL . min(-1) in women comp ared with 25,595 +/- 10,245 in men and lower than after administration of r egular-release verapamil (63,055 +/- 24,411 for women and 34,686 +/- 25,279 in men; P = .05 for sex-related effect and P < .02 for formulation effect) . AUC ratios of norverapamil (N-demethylated metabolite) to verapamil after administration of sustained-release verapamil were 1.43 +/- 0.26 in women compared with 1.74 +/- 0.41 in men and 1.43 +/- 0.26 in women compared with 1.78 +/- 0.37 in men after administration of regular-release verapamil (P = .1 for sex-related effect and P = .9 for formulation effect). Apparent or al clearance was 43 +/- 15 mL/min/kg in women compared with 75 +/- 29 in me n after administration of sustained-release verapamil and 35 +/- 16 mL/min/ kg in women compared with 65 +/- 31 in men after administration of regular- release verapamil (P < .05 for sex-related effect and P < .02 for formulati on effect). Apparent oral clearance of both regular- and sustained-release formulations of verapamil was faster in men compared with women in contrast to findings after intravenous administration of verapamil, suggesting that intestinal processes are a factor in sex-specific difference in drug clear ance. Greater verapamil and norverapamil bioavailability after administrati on of regular- compared with sustained-release verapamil also suggests satu rable processes at the intestinal level.