Human pharmacokinetics of orally administered (24 R)-hydroxycalcidiol.
To gain an insight in the regulation of (24R)-hydroxycalcidiol, we studied the pharmacokinetics of orally administered (24R)-hydroxycalcidiol in 6 healthy subjects without calcium supplementation, in 4 healthy subjects with calcium supplementation and in 6 patients with primary hyperparathyroidism. Various quantities related to calcium and vitamin D metabolism were also monitored. In the healthy subjects without calcium supplementation, the basal (24R)-hydroxycalcidiol concentration (Cb) in serum was 2.4 +/- 0.8 nmol/l (mean +/- SD, n = 5), the terminal serum half-time (t 1/2) 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 administration, possibly due to binding by intestinal cells or (partial) uptake by the lymph system. In the calcium-supplemented healthy subjects, the pharmacokinetic quantities were not significantly different while the area under the serum concentration-time curve and the estimated bioavailability were significantly decreased. Basal concentration (Cb), production rate and the production rate/[calcidiol] ratio were significantly lower in patients with primary hyperparathyroidism but t 1/2 was unchanged. Exogenous (24R)-hydroxycalcidiol had no clear effect on calcium and vitamin D metabolism. In conclusion, a) exogenous (24R)-hydroxycalcidiol has no clear effect on calcium and vitamin D metabolism, b) clearance and production rate of (24R)-hydroxycalcidiol are not affected 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.
Department of Internal Medicine, Free University Hospital, Amsterdam, The Netherlands.
O R
OR
Leeuwenkamp
H E
HE
van der Wiel
P
P
Lips
W J
WJ
van der Vijgh
R
R
Barto
H
H
Greuter
J C
JC
Netelenbos
D015650:24,25-Dihydroxyvitamin D 3; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D001835:Body Weight; D002112:Calcifediol / Q000097:blood; D002118:Calcium / Q000008:administration & dosage* / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006961:Hyperparathyroidism / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D014807:Vitamin D / Q000378:metabolism
D006887:Hydroxycholecalciferols; C030711:24-hydroxyvitamin D3; D014807:Vitamin D; D015650:24,25-Dihydroxyvitamin D 3; D002112:Calcifediol; D002118:Calcium