Pharmacokinetics of active vitamins D3, 1 α-hdyroxyvitamin D3 and 1 α, 25-dihydroxyvitamin D3 in patients on chronic hemodialysis

Two active forms of vitamin D3, 1α, 25-dihydroxyvitamin D3 (1 α,25 [OH] 2D3) and 1 α-hydroxyvitamin D3 (1α, [OH] D3) are widely used for treating osteodystrophy in patients with chronic renal failure. Since the pharmacokinetics of these agents during longterm oral administration are unclear, we measured the circulating concentrations of 1α, 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 1α, (OH) D3 (0.5 μg), the administration of a single dose (2 μg) of 1α, (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 1α, 25 (OH) 2D3 (0.25 μg), a single dose of 1α, 25 (OH) 2D3 (1 μg) 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(T1/2) of circulating plasma 1 α, 25 (OH) 2D. The overall basal concentration of 1α, 25 (OH) 2D achieved by 1α, (OH) D3 after 12 weeks of administration was cumulative, but this effect was not observed in patients on 1α, 25 (OH) 2D3. These data indicate that the pharmacokinetics of the twoforms of active vitamin D3 did not differ as to peak increment and T1/2 except for the AUC, even after long-term dosage. It is suggested that 1α, (OH) D3 may be more effective in maintaining a consistent circulating level of 1α, 25 (OH) 2D in patients on chronic hemodialysis.