HUMAN PHARMACOKINETICS OF ORALLY-ADMINISTERED (24R)-HYDROXYCALCIDIOL

To gain an insight in the regulation of (24R)-hydroxycalcidiol, we stu died the pharmacokinetics of orally administered (24R)-hydroxycalcidio l in 6 healthy subjects without calcium supplementation, in 4 healthy subjects with calcium supplementation and in 6 patients with primary h yperparathyroidism. Various quantities related to calcium and vitamin D metabolism were also monitored. In the healthy subjects without calc ium supplementation, the basal (24R)-hydroxycalcidiol concentration (C b) in serum was 2.4 +/- 0.8 nmol/l (mean +/- SD, n = 5), the terminal serum half-time (t1/2) 7.2 +/- 1.4 days, the production rate 0.05 +/- 0.01 nmol/kg . day, and the production rate/[calcidiol] ratio (1.5 +/- 0.4 x 10(-3) l/kg . day). In the healthy subjects studied, the serum concentration vs time curves exhibited a second maximum after administ ration, possibly due to binding by intestinal cells or (partial) uptak e by the lymph system. In the calcium-supplemented healthy subjects, t he pharmacokinetic quantities were not significantly different while t he area under the serum concentration-time curve and the estimated bio availability were significantly decreased. Basal concentration (C(b)), production rate and the production rate/[calcidiol] ratio were signif icantly lower in patients with primary hyperparathyroidism but t1/2 wa s unchanged. Exogenous (24R)-hydroxycalcidiol had no clear effect on c alcium and vitamin D metabolism. In conclusion, a) exogenous (24R)-hyd roxycalcidiol has no clear effect on calcium and vitamin D metabolism, b) clearance and production rate of (24R)-hydroxycalcidiol are not af fected by calcium supplementation, c) bioavailability is lower in the calcium-supplemented state, d) basal concentration (Cb) and production rate are significantly decreased in patients with hyperparathyroidism .