A comparison between daily and thrice-weekly i.v. administration of 1,25-dihydroxy-22-oxavitamin D(3) regarding suppression of parathyroid hormone secretion and calcaemic action in uraemic rats.
BACKGROUND
1,25-Dihydroxy-22-oxavitamin D(3) (22-oxacalcitriol, OCT) is an analogue of 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3), calcitriol) with less calcaemic activity, thus more suitable than 1,25(OH)(2)D(3) for the control of parathyroid hormone (PTH) secretion in chronic dialysis patients. As the low-calcaemic action of OCT has been mainly attributed to its short half-life in the blood stream, the number of doses per week is the key factor to effective OCT therapy toward suppression of PTH secretion and hypercalcaemia. Thus, we investigated a comparison between daily and thrice-weekly i.v. administration of OCT regarding suppression of PTH secretion and calcaemic action in 5/6 nephrectomized rats as a model for chronic renal failure.


METHODS
Model rats of chronic renal failure were made by 5/6 nephrectomy. At 3 months after surgery, they were administered either vehicle or OCT intravenously, daily (0.125 or 0.625 microg/kg) or thrice-weekly (0.6 or 3.0 microg/kg) for 2 weeks.


RESULTS
The data show that 0.625 microg/kg/day (=4.375 microg/kg/week) suppresses PTH secretion with significant increase in calcium levels at 24 h after the final administration, on the other hand, 3.0 microg/kg/ thrice-weekly (=9.0 microg/kg/week) suppresses PTH secretion, although moderate compared with 0.625 microg/kg/day, with a slight (not significant) increase in calcium.


CONCLUSIONS
The current clinical mode of OCT therapy, i.v. thrice-weekly administration, is a practically recommendable protocol.
Hirata
Michinori
M
Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co, Ltd, Gotemba, Shizuoka, Japan. hiratamcn@chugai-pharm.co.jp
Endo
Koichi
K
Ohkawa
Hiroyuki
H
Kumaki
Kenji
K
Kubodera
Noboru
N
Slatopolsky
Eduardo
E
Kurokawa
Kiyoshi
K
Fukagawa
Masafumi
M
D000818:Animals; D001806:Blood Urea Nitrogen; D001835:Body Weight; D002117:Calcitriol / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood*; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007275:Injections, Intravenous; D008297:Male; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010710:Phosphates / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000097:blood / Q000188:drug therapy*
D010281:Parathyroid Hormone; D010710:Phosphates; D003404:Creatinine; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium