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Serum calcitriol and parathyroid hormone levels following prolonged infusion of calcitriol in vitamin D replete and depleted rabbits.

The objectives of this study are (1) to determine if serum calcitriol levels resulting from calcitriol infusion by subcutaneously implanted osmotic pumps are in proportion to dose, (2) to determine if such serum levels remain steady during the "pump-life" and (3) to determine if these increased calcitriol levels have an effect on serum parathyroid hormone (PTH) levels. A general objective of the study is to define a model whereby agents (calcitriol, and parathyroid hormone) suspected of enhancing absorption of metals other than calcium from the gastrointestinal tract could be evaluated individually by the levels of these hormones present in serum at a series of intervals during calcitriol infusion by osmotic pump. Calcitriol was infused into rabbits by subcutaneously implanted osmotic pumps at 3 different dosages (30, 60, and 100 IU/day) for 7 days and one dose (60 IU/day) for a 28 day period. The serum calcitriol levels initially rose markedly in all experimental rabbits in proportion to infused dosage and peaked at 3 days. The quantitative relationship between infused calcitriol and serum calcitriol at 3-5 days showed a correlation coefficient of 0.977 (P less than 0.005) for rabbits receiving the 7 day pumps with the 3 different dosages. There was subsequent decline of serum calcitriol which continued for the remainder of the pump-life, suggesting acceleration of degradation mechanisms. There was a sharp reduction in serum parathyroid hormone (PTH) levels 3-5 days after starting the calcitriol infusion, which was interpreted to result from direct suppression of PTH synthesis by calcitriol and/or the feedback effect of enhanced intestinal calcium absorption. Rabbits which had been depleted of vitamin D prior to implantation of the 28 day osmotic pumps showed a similar pattern of serum calcitriol and PTH. Multiple analyses within a single rabbit showed a reciprocal relationship between the serum calcitriol and PTH during the 28 days. There was a statistically significant negative correlation between these parameters (r = 0.635, P less than 0.05). The data indicate that despite a constant rate of infusion of calcitriol by osmotic pump, the levels of serum calcitriol and parathyroid hormone do not remain constant, but rather undergo marked changes. These findings demonstrate the necessity of monitoring blood levels, even in studies in which animals receive a constant infusion of calcitriol.