Effects of gender on vitamin C pharmacokinetics in man

The pharmacokinetics of vitamin C (VC) were compared in young and elderly male and female subjects following 500 mg oral doses to each subject in two states of VC nutriture: a depleted state achieved by 4-5 weeks on a diet containing less than 10 mg VC/day and a supplemented state which was achieved following 500 mg/day doses of VC for 3 weeks. The males were taller and heavier than their female counterparts and consequently had a greater body surface area (BSA). The body mass index (BMI) and fat mass did not differ between genders within an age group, whereas only the young females exhibited a greater percent body fat. The males exhibited a larger fat-free mass (FFM) than the females. None of the pharmacokinetic parameters differed due to gender in depleted subjects. In the supplemented state the female subjects exhibited a significantly greater peak VC concentration (Cmax), a longer absorption lag time (tlag), apparent volume of distribution (AVd) in L/kg, clearance (CL) in ml/hr/kg, and renal clearance (CLr) in ml/hr/kg. When AVd, CL, and CLr were expressed in absolute terms (i.e., L or ml/min), no gender-related differences were observed. A stepwise multiple linear regression indicated that Cmax was inversely linearly related to body weight, tlag was directly related to BSA and dose, and AVd (L/kg) was inversely linearly related to BSA. CL (ml/hr/kg) and CLr (ml/hr/kg) were not significantly related to any of the body composition parameters examined. Overall, these results indicate that there are few gender-related differences in the pharmacokinetics of VC in humans and that a portion of the observed differences can be explained by body composition differences between the sexes.