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

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.