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Nephrol Dial Transplant (2002) 17: 37-40
© 2002 European Renal Association-European Dialysis and Transplant Association


A comparison between daily and thrice-weekly i.v. administration of 1,25-dihydroxy-22-oxavitamin D3 regarding suppression of parathyroid hormone secretion and calcaemic action in uraemic rats

Michinori Hirata1,, Koichi Endo1, Hiroyuki Ohkawa1, Kenji Kumaki1, Noboru Kubodera1, Eduardo Slatopolsky2, Kiyoshi Kurokawa3 and Masafumi Fukagawa4

1 Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, Gotemba, Shizuoka, Japan, 2 Department of Internal Medicine, Renal Division, Washington University School of Medicine, St Louis, Missouri, USA, 3 Tokai University School of Medicine, Isehara, Japan and 4 Division of Nephrology and Dialysis Center, Kobe University School of Medicine, Kobe, Japan

Abstract

Background. 1,25-Dihydroxy-22-oxavitamin D3 (22-oxacalcitriol, OCT) is an analogue of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, calcitriol) with less calcaemic activity, thus more suitable than 1,25(OH)2D3 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 µg/kg) or thrice-weekly (0.6 or 3.0 µg/kg) for 2 weeks.

Results. The data show that 0.625 µg/kg/day (=4.375 µg/kg/week) suppresses PTH secretion with significant increase in calcium levels at 24 h after the final administration, on the other hand, 3.0 µg/kg/ thrice-weekly (=9.0 µg/kg/week) suppresses PTH secretion, although moderate compared with 0.625 µg/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.

Keywords: calcaemic action; OCT; parathyroid hormone; secondary hyperparathyroidism; uraemia; vitamin D analogue

Notes

Correspondence and offprint requests to: Michinori Hirata, PhD, Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, 1-135 Gotemba, Shizuoka 412-8513, Japan. Email: hiratamcn{at}chugai\|[hyphen]\|pharm.co.jp


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