A comparison between 1,25-dihydroxy-22-oxavitamin D(3) and 1,25-dihydroxyvitamin D(3) regarding suppression of parathyroid hormone secretion and calcaemic action.
BACKGROUND
Since Slatopolsky et al. (J Clin Invest 1984; 74: 2136-2143) reported the effect of active vitamin D, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), on secondary hyperparathyroidism (2HPT) which accompanies chronic renal failure, there have been several studies of the therapeutic effects of 1,25(OH)(2)D(3) in this disease. Although parathyroid hormone (PTH) is suppressed by treatment with 1,25(OH)(2)D(3), long-term treatment with 1,25(OH)(2)D(3) tends to induce hypercalcaemia. Therefore, an analogue of 1,25(OH)(2)D(3), 1,25-dihydroxy-22-oxavitamin D(3) (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)(2)D(3) 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)(2)D(3) 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)(2)D(3) 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)(2)D(3), 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)(2)D(3) 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.
Hirata
Michinori
M
Fuji Gotemba Research Labs, Chugai Pharmaceutical Co, Ltd, Shizuoka, Japan.
Endo
Koichi
K
Katsumata
Kyoko
K
Ichikawa
Fumihiko
F
Kubodera
Noboru
N
Fukagawa
Masafumi
M
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002117:Calcitriol / Q000031:analogs & derivatives / Q000097:blood / Q000494:pharmacology*; D002118:Calcium / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000188:drug therapy*; D008297:Male; D009392:Nephrectomy; D010281:Parathyroid Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014511:Uremia / Q000188:drug therapy*
D010281:Parathyroid Hormone; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium