Pharmacodynamics and Drug Action
Clinical Pharmacology & Therapeutics (1999) 66, 609–616; doi: 10.1053/cp.1999.v66.103169001
Chronotherapy of high-dose 1,25-dihydroxyvitamin D3 in hemodialysis patients with secondary hyperparathyroidism: A single-dose study
Shuichi Tsuruoka MD1, Koh-ichi Sugimoto MD1, Masami Ohmori MD1, Atsuhiro Kawaguchi PharmD1, Tetsuo Saito MD1 and Akio Fujimura MD1
1Department of Clinical Pharmacology, Jichi Medical School, Minamikawachi, and Moka Hospital, Moka, Tochigi, Japan.
Correspondence: Shuichi Tsuruoka, MD, Department of Clinical Pharmacology, Jichi Medical School, 3311 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan. E-mail: tsuru@jichi.ac.jp
Received 30 June 1999; Accepted 22 September 1999.
Abstract
Background: A high-dose oral intermittent vitamin D (pulse therapy) is widely used for the treatment of secondary hyperparathyroidism associated with kidney failure. However, hypercalcemia by vitamin D sometimes interrupts this treatment. Because serum calcium concentration possesses a circadian rhythm, a chronopharmacologic approach of vitamin D may have merit for avoidance of adverse reactions.
Methods: Six female secondary hyperparathyroidism patients receiving maintenance hemodialysis received a single oral dose of 2 
g 1,25-dihydroxyvitamin D3 at either 8 AM or 8 PM in a crossover design. Serum concentrations of ionized and total calcium, phosphate, and vitamin D3 were determined for a 48-hour period after administration. We also measured serum intact parathyroid hormone before and 48 hours after dosing as an index for efficacy.
Results: A single oral administration of the drug caused an increase in concentration of ionized calcium, serum calcium, and phosphate. However, the area under concentration–time curve from zero to 48 hours [AUC(0-48)] and peak concentration of these variables were markedly lower after dosing at 8 PM. Predose concentrations of these variables were lower at night. The AUC(0-48) of serum vitamin D3 of the morning and night trials did not differ significantly. Reduction of intact parathyroid hormone concentration was also similar between the two trials.
Conclusion: The administration of vitamin D3 at night may reduce the occurrence of hypercalcemia and hyperphosphatemia in patients with secondary hyperparathyroidism, whereas the pharmacokinetics and intact parathyroid hormone–lowering effect of the drug does not vary with dosing time.
