Effect of hemodialysis on the pharmacokinetics of 19-nor-1α,25-dihydroxyvitamin D2

The vitamin D-2 analogue 19-nor-1 alpha,25-dihydroxyvitamin D-2 (paricalcitol) has been tested for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease. Clinical studies have shown that paricalcitol reduces serum parathyroid hormone (PTH) levels with minimal potential to cause hypercalcemia, a common side effect of vitamin D-3 therapy. Paricalcitol is typically administered intravenously after hemodialysis (HD). Because the administration of paricalcitol before or during dialysis would be desirable, the effect of HD on paricalcitol pharmacokinetics was investigated. Six patients requiring HD received a single dose of paricalcitol, 0.08 mu g/kg, intravenously approximately 2 hours before HD, and blood samples were collected by venipuncture immediately before and 15 minutes after HD. Also, pairs of pre- and postdialyzer blood samples were collected approximately 1 and 2 hours after the start of HD. Plasma concentrations of paricalcitol in the samples were determined by a specific high-performance liquid chromatography (HPLC)/radioreceptor assay (RRA) with a lower limit of quantification of 40 pg/mL. Compared with previous pharmacokinetic studies in HD patients, plasma concentrations (100 to 250 pg/mL) during the 4-hour period were consistent with predicted values for this dose, and there was no apparent increase in paricalcitol clearance during HD. Pre- and postdialyzer plasma concentrations of paricalcitol were compared statistically using a paired t-test. Postdialyzer concentrations tended to be slightly higher than those predialyzer, but the differences were not statistically significant (P = 0.11). Thus, HD essentially had no effect on plasma concentrations of paricalcitol, suggesting that paricalcitol can be administered at any time during dialysis. (C) 1998 by the National Kidney Foundation, Inc.