Pharmacokinetics of active vitamins D3, 1 alpha-hydroxyvitamin D3 and 1 alpha, 25-dihydroxyvitamin D3 in patients on chronic hemodialysis.
Two active forms of vitamin D3, 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25 [OH] 2D3) and 1 alpha-hydroxyvitamin D3 (1 alpha, [OH] D3) are widely used for treating osteodystrophy in patients with chronic renal failure. Since the pharmacokinetics of these agents during long-term oral administration are unclear, we measured the circulating concentrations of 1 alpha, 25 (OH) 2D before and after their long-term oral administration in patients receiving maintenance hemodialysis. After 12 weeks of treatment with a daily dose of 1 alpha, (OH) D3 (0.5 micrograms), the administration of a single dose (2 micrograms) of 1 alpha, (OH) D3 showed that the area under the curve over 24 h (AUC) was increased significantly compared with day 1 of therapy. In contrast, after the treatment with a daily dose of 1 alpha, 25 (OH) 2D3 (0.25 micrograms), a single dose of 1 alpha, 25 (OH) 2D3 (1 microgram) did not exhibit this effect on the AUC. A single dose of each agent produced no significant change in either the peak increment above basal values or the elimination half-time (T 1/2) of circulating plasma 1 alpha, 25 (OH) 2D. The overall basal concentration of 1 alpha, 25 (OH) 2D achieved by 1 alpha, (OH) D3 after 12 weeks of administration was cumulative, but this effect was not observed in patients on 1 alpha, 25 (OH) 2D3. These data indicate that the pharmacokinetics of the two forms of active vitamin D3 did not differ as to peak increment and T1/2 except for the AUC, even after long-term dosage.(ABSTRACT TRUNCATED AT 250 WORDS)
Kimura
Y
Y
Department of Internal Medicine, Jikei University School of Medicine, Kashiwa Hospital, Chiba, Japan.
Nakayama
M
M
Kuriyama
S
S
Watanabe
S
S
Kawaguchi
Y
Y
Sakai
O
O
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002117:Calcitriol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy*; D006435:Renal Dialysis; D013997:Time Factors
D006887:Hydroxycholecalciferols; D002117:Calcitriol; C008088:alfacalcidol