Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients.

Because intravenous (iv) calcitriol has greater bioavailability than oral calcitriol, it may be more efficacious in suppressing parathyroid hormone (PTH) secretion. In this study, the pharmacokinetics and efficacy of pulse oral and i.v. calcitriol were compared. Patients were randomized to receive 2 micrograms of i.v. or oral calcitriol after each dialysis. Two pharmacokinetic studies (PK1, PK2) were performed 10 days apart, during which the patients received calcitriol after each dialysis. Calcitriol bioavailability was determined from the area under the curve (AUCtime interval (hours) in pg/mL per h). After the PK phase, PTH was lowered to < 200 pg/mL by titrating calcitriol to a maximum of 12 micrograms/wk over 4 wk. Calcitriol was then maintained for another 18 wk unless serum calcium exceeded 11.5 mg/dL or Ca x P product exceeded 70; when these limits were reached, calcitriol was held and then restarted at a lower dose. After i.v. administration, peak serum calcitriol exceeded that achieved orally but by 1 h, calcitriol levels were similar. The AUC0-0.5 (105 +/- 12, i.v.; 9 +/- 4, oral) and AUC0.5-1 (68 +/- 6, i.v.; 30 +/- 7, oral) were higher with i.v. (P < 0.05), but cumulative AUC0-48 did not differ. Individual t1/2 values ranged from 10 to 129 h for PK1 and from 10 to 50 h for PK2. The t1/2 for oral calcitriol was 38 +/- 14 h for PK1 and 30 +/- 4 h for PK2 (not significant (NS)). The t1/2 for i.v. calcitriol was 26 +/- 5 h for PK1 and 19 +/- 3 h for PK2 (NS, PK1 versus PK2 and oral versus i.v.). When the PK1 oral and i.v. data were combined, the mean t1/2 was 32 +/- 7 h whereas the t1/2 for PK2 (oral and i.v.) was 22 +/- 3 h (P < 0.05). Baseline PTH levels were 510 +/- 90 pg/mL and 499 +/- 79 pg/mL, oral and i.v., respectively. Serum PTH level at 22 wk was not different between oral and i.v. groups, 153 +/- 38 pg/mL and 214 +/- 124 pg/mL in i.v. (NS). The percentage of PTH suppression was 66 +/- 7.4% in the oral group and 69 +/- 12% in the i.v. group (NS). A major degree of serum iPTH suppression occurred during the initial 4 wk of treatment, concomitant with a rise in serum calcium levels. Adverse effects were similar between groups, as were the average dosages of calcitriol and phosphate binders. In conclusion, the efficacy of intravenous and pulse oral calcitriol were similar in hemodialysis patients with secondary hyperparathyroidism. The early rise in serum calcium levels observed with treatment may have contributed significantly to the suppression of serum iPTH levels. The difference in bio-availability between the different routes does not have a clinically apparent effect. The t1/2 varied widely among individuals, whereas exposure to calcitriol may decrease the t1/2.

RCT Entities:   Population Interventions Outcomes