Dosing time-dependent variation in the hypocalcemic effect of calcitonin in rat.
Dosing time-dependent variation in the hypocalcemic effect of salmon calcitonin was examined in rats under a 12-h light-dark cycle. In both a single-dosing study with normal rats and a repeated-dosing study with hypercalcemic rats (induced by chronic vitamin-D dosing), we consistently observed that the hypocalcemic effect of calcitonin was greater when the drug was given at 14 h after lights on than that at 2 h after lights on. The reduction in urinary deoxypyridinoline excretion, a marker of bone resorption, was also greater when calcitonin was given at 14 h after lights on. Urinary excretion of Ca was not affected by the drug. Pharmacokinetic profiles of calcitonin after a single dosing did not differ between the two trials. These results indicate that the hypocalcemic effect of calcitonin is greater after dosing in the early dark phase (14 h after lights on) than after dosing in the early light phase (2 h after lights on). A time-dependent variation in the sensitivity to the drug of osteoclasts, but not renal tissues, may be involved in the mechanism of this event.
Nishiki
Kenta
K
Department of Clinical Pharmacology, Jichi Medical School, 3311 Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan.
Tsuruoka
Shuichi
S
Wakaumi
Michi
M
Yamamoto
Hisashi
H
Koyama
Akio
A
Fujimura
Akio
A
D000596:Amino Acids / Q000652:urine; D000818:Animals; D002116:Calcitonin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002118:Calcium / Q000097:blood* / Q000652:urine; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006996:Hypocalcemia / Q000097:blood* / Q000139:chemically induced / Q000652:urine; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000596:Amino Acids; C036020:deoxypyridinoline; D002116:Calcitonin; D002118:Calcium