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Chronotherapy of high‐dose 1,25‐dihydroxyvitamin D 3 in hemodialysis patients with secondary hyperparathyroidism: A single‐dose study
Author(s) -
Tsuruoka Shuichi,
Sugimoto Kohichi,
Ohmori Masami,
Kawaguchi Atsuhiro,
Saito Tetsuo,
Fujimura Akio
Publication year - 1999
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1053/cp.1999.v66.103169001
Subject(s) - secondary hyperparathyroidism , parathyroid hormone , medicine , endocrinology , pharmacokinetics , hyperphosphatemia , hemodialysis , dosing , calcium metabolism , chronotherapy (sleep phase) , hyperparathyroidism , calcitriol , bedtime , vitamin d and neurology , urology , calcium , morning
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 μg 1,25‐dihydroxyvitamin D 3 at either 8 AM or 8 PM in a crossover design. Serum concentrations of ionized and total calcium, phosphate, and vitamin D 3 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 D 3 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 D 3 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. Clinical Pharmacology & Therapeutics (1999) 66 , 609–616; doi: 10.1053/cp.1999.v66.103169001