Adsorption of oxacalcitriol by polysulphone haemodialyser in patients with secondary hyperparathyroidism

Abstract

Br J Clin PharmacolBritish Journal of Clinical Pharmacology DOI:10.1111DOI:10. /j.1365DOI:10. -2125DOI:10. .2004 AimsThis study was undertaken to evaluate removal of 22-oxacalcitriol (OCT), an active and intravenously used vitamin D3 analogue with less calcaemic activity, by polysulphone haemodialyser in vivo and in vitro . We further compared the pharmacodynamic efficacy [suppression of intact parathyroid hormone (iPTH)] when g iven intravenously either during or at the end of the haemodialysis. Methods(i) Drug clearance by the polysulphone dialyser was measured during a single continuous infusion (5 m g) for 30 min into the arterial side of the dialyser in endstage renal failure patients with secondary hyperparathyroidism ( n = 7). (ii) The drug adsorption by the hollowfibre membrane during incubation for 30 min was measured in vitro . (iii) To evaluate efficacy, the drug was given (i.v. bolus) during or at the end of haemodialysis for 4 weeks in a cross-over fashion with a washout period of 8 weeks ( n = 9). Serum Ca 2 + , phosphate (P) and iPTH concentrations just before the initiation of the dialysis were monitored every week. Results(i) OCT was significantly cleared by the polysulphone haemodialyser, but the clearance declined in a time-dependent manner to approach zero at 30 min. Arterial (at the place between the drug infusion site and the haemodialyser column) drug concentrations did not change during the infusion (mean = 2064 ± 233 pg ml -1 ). Venous (just after the dialyser) drug concentrations at 10 min after the infusion were significantly lower than those of the arterial side (mean = 784 ± 84 pg ml -1 ); however, they increased with time and reached those of the arterial side at 30 min. (ii) In vitro , OCT was adsorbed by the membrane. The amount of adsorption was concentration-dependent and was lower in the presence of human serum (55 ± 4% without and 23 ± 4% with serum at 600 pg ml -1 of OCT). (iii) Although serum Ca 2 + and P increased and iPTH decreased by both treatment regimens (i.e. OCT administered either during or at the end of haemodialysis), these changes did not significantly differ. Mean differences (and 95% confidence interval) of Ca 2 + , P, and iPTH at the end of the trial were 0.03 ( -0.04, 0.09) m M , 0.41 ( -0.43, 1.26) mg dl -1 and 38 ( -42, 88) pg ml -1 , respectively. ConclusionOCT is adsorbed by polysulphone dialyser in vitro and in vivo . However, the pharmacodynamic effectiveness was largely independent of the administration reg imen of OCT given either during or at the end of haemodialysis. Adsorption of oxacalcitriol by haemodialyserBr J Clin Pharmacol 58 :5 489

Polymer Membrane and Cell Models for Drug Discovery

“…As reported, oxacalcitriol, a vitamin D3 analogue, was severely adsorbed on polysulfone haemodialyser [114]. Unger and coworkers described the high capacity of adsorption of hydrophobic drugs and hormones (with high octanol/water partition coefficient) on bioartificial liver [115].…”

PPO/PEO modified hollow fiber membranes improved sensitivity of 3D cultured hepatocytes to drug toxicity via suppressing drug adsorption on membranes

“…on polymer membranes used in artificial organs was also found to impair the drugs concentration in blood (e.g. oxacalcitriol and lidocaine) and harm patients' health during clinical therapy [7,8].…”