Nephrol Dial Transplant (2002) 17: 41-45
© 2002 European Renal Association-European Dialysis and Transplant Association
A comparison between 1,25-dihydroxy-22-oxavitamin D3 and 1,25-dihydroxyvitamin D3 regarding suppression of parathyroid hormone secretion and calcaemic action
1 Fuji Gotemba Research Labs, Chugai Pharmaceutical Co., Ltd, Shizuoka, Japan and 2 Kobe University School of Medicine, Division of Nephrology and Dialysis Center, Kobe, Japan
Abstract
Background. Since Slatopolsky et al. (J Clin Invest 1984; 74: 2136–2143) reported the effect of active vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), on secondary hyperparathyroidism (2HPT) which accompanies chronic renal failure, there have been several studies of the therapeutic effects of 1,25(OH)2D3 in this disease. Although parathyroid hormone (PTH) is suppressed by treatment with 1,25(OH)2D3, long-term treatment with 1,25(OH)2D3 tends to induce hypercalcaemia. Therefore, an analogue of 1,25(OH)2D3, 1,25-dihydroxy-22-oxavitamin D3 (22-oxacalcitriol, OCT) with less calcaemic activity, was developed for the treatment of 2HPT.
Methods. In order to clarify the differences between the effects of 1,25(OH)2D3 and OCT on 2HPT associated with chronic renal failure, these compounds were administered by intermittent i.v. injection for 2 weeks in rats with mild to moderate uraemia.
Results. 1,25(OH)2D3 markedly suppressed PTH levels, but increased serum calcium (Ca). OCT also markedly suppressed PTH levels, but induced only a slight increase in serum Ca. 1,25(OH)2D3 caused a dose-dependent decrease in body weight, whereas OCT had no effect on body weight in uraemic rats. Based on those doses of OCT and 1,25(OH)2D3, which resulted in a 60% suppression of PTH, and induced hypercalcaemia, we consider the relative ratios for efficacy and Ca-elevating activity between OCT and 1,25(OH)2D3 to be 1:8 and 1:48, respectively.
Conclusions. OCT suppressed PTH levels with a slight increase in serum Ca without changing the body weight in uraemic rats. This observation suggests that OCT might be a useful vitamin D analogue for 2HPT management in long-term clinical treatment.
Keywords: calcaemic action; 22-oxacalcitriol; OCT; 1,25(OH)2D3; parathyroid hormone; secondary hyperparathyroidism
Notes
Correspondence and offprint requests to: Koichi Endo, PhD, Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd, 1-135 Komakado, Gotemba, Shizuoka 412-8513, Japan. Email: endokui{at}chugai\|[hyphen]\|pharm.co.jp
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