Pharmacokinetics of 1 alpha-hydroxycholecalciferol after intraperitoneal, intravenous and oral administration in patients undergoing peritoneal dialysis.
Intravenous (i.v.) injection of vitamin D3 has a well known suppressive effect on the release of parathyroid hormone. However, the i.v. route is inconvenient in patients undergoing peritoneal dialysis. Moreover, no study has been published on the pharmacokinetics of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) after intraperitoneal (IP), i.v. and oral administration. Therefore, the appearance of 1,25-(OH)2D3 after administration of 1 alpha-OHD3 was studied in 8 peritoneal dialysis patients. Open, prospective, randomized cross-over design with single doses of 1 alpha-OHD3 (80 ng/kg BW) given on 3 separate occasions either IP, i.v. or oral was applied. After the administration of 1 alpha-OHD3, blood was collected at baseline and 0.5, 1, 2, 3, 4, 6, 12 and 24 h for measurement of circulating 1,25-(OH)2D3. A one compartment model with first order absorption and elimination (Cpl = Be-ke*t-Ae-ka*t) was fitted to the concentrations following i.v. administration. Following IP and oral administration the concentrations did not reach maximum levels within the time of blood sampling. In all cases, the 24 h area under the time/concentration curve for 1,25-(OH)2D3 (AUC24) was calculated using the trapezoidal method. Residual areas were calculated using the terminal slope from i.v. administration, and added to AUC24 giving AUC0-->infinity. After i.v. administration A, ka, B, ke, t1/2, AUC24 and AUC0-->infinity were (mean +/- SD) 62.9 +/- 16.4 pg/ml, 0.76 +/- 0.30 h-1, 71.6 +/- 14.7 pg/ml, 0.017 +/- 0.015 h-1, 109.4 +/- 129.5 h, 1315.8 +/- 236.9 pg/ml x h and 10322.2 +/- 11473.7 pg/ml x h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Joffe
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P
Department of Nephrology, Herlev County Hospital, University of Copenhagen, Denmark.
Cintin
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Ladefoged
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SD
Rasmussen
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D000284:Administration, Oral; D001682:Biological Availability; D002117:Calcitriol / Q000493:pharmacokinetics; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000517:prevention & control; D005260:Female; D006801:Humans; D006887:Hydroxycholecalciferols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007263:Infusions, Parenteral; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D010530:Peritoneal Dialysis; D011446:Prospective Studies
D006887:Hydroxycholecalciferols; D002117:Calcitriol; C008088:alfacalcidol