PHARMACOKINETICS OF CALCITRIOL IN CONTINUOUS AMBULATORY AND CYCLING PERITONEAL-DIALYSIS PATIENTS

Oral calcitriol is commonly used for the treatment of secondary hyperparathyroidism in patients undergoing long-term dialysis, but it has been suggested that intravenous (IV) or intraperitoneal (IP) administration enhances the therapeutic efficacy of the sterol. To examine potential mechanims for this difference, the bioavailability of calcitriol was evaluated after single oral (PO), IV, and IP doses of 60 ng/kg in each of six adolescent patients with osteitis fibrosa undergoing continuous ambulatory peritoneal dialysis (CAPO) or continuous cycling peritoneal dialysis (CCPD). Serum calcitriol levels were 3.6 ± 4.3, 8.2 ± 7.5, and 2.5 ± 3.0 pg/mL, respectively, before IV, PO, and IP doses of the sterol; these values increased to similar levels at 24 hours: 55.6 ± 14.6 pg/mL after PO, 56.4 ± 17.6 pg/mL after IV, and 53.8 ± 20.1 pg/mL after IP. Serum calcitriol levels were higher 1, 3, and 6 hours after IV injections than after PO or IP doses; values thereafter did not differ among groups. The bioavailability of calcitriol, determined from the 24-hour area under the curve (AUC0-24) for the increase in serum calcitriol concentration above baseline values was 50% to 60% greater after IV, 2,340 ± 523 pg mL-1 h-1, than after PO, 1,442 ± 467 pg mL-1 h-1, or IP, 1,562 ± 477 pg mL-1 h-1, dosages, P < 0.05. These differences were due to higher values for AUC during the first 6 hours after calcitriol administration. Although IP calcitriol did not increase sterol bioavailability, radioisotope tracer studies indicated that 35% to 40% of the hormone adheres to plastic components of the peritoneal dialysate delivery system. By modifying the technique of IP calcitriol instillation and by increasing the dose to 120 ng/kg, serum calcitriol levels were equal to or greater than the values obtained after IV injections and the AUC increased by 62% compared with IV doses (60 ng/kg). Altering the technique of IP calcitriol administration may enhance the therapeutic efficacy of the hormone in the treatment of secondary hyperparathyroidism. © 1990, National Kidney Foundation Inc.. All rights reserved.