Nephrol Dial Transplant (2003) 18: 750-758
© 2003 European Renal Association-European Dialysis and Transplant Association
Pharmacokinetics of doxercalciferol, a new vitamin D analogue that lowers parathyroid hormone
1 Department of Biopharmaceutical Sciences, University of California, San Francisco, CA and 2 Bone Care International, Inc., Middleton, WI, USA
Background. This is the first detailed pharmacokinetic report published on the administration of doxercalciferol [1
(OH)D2] recently introduced to treat secondary hyperparathyroidism.
Methods. 1(OH)D2 was administered in a range of single and multiple doses to volunteers with and without normal renal and/or hepatic function. Subsequent serial blood samples were assayed by HPLC/radioimmunoassay for the metabolite 1,25-dihydroxyvitamin D2 [1,25(OH)2D2], the major active species.
Results. Bioavailability of 1,25(OH)2D2 from a single 5 µg 1(OH)D2 oral-capsule dose was estimated to be normally 
42% of that from a 5 µg intravenous injection. Steady-state serum concentrations of 1,25(OH)2D2 were attainable within 8 day, and fluctuated 2.5-fold from peak to trough when oral 1(OH)D2 doses were taken every second day, and the terminal half-life was 34±14 h. Mean steady-state serum concentrations rose less than proportionally (from 20 to 45 pg/ml) on increasing oral 1(OH)D2 doses from 5 to 15 µg every 48 h. Renal patients showed 39±37% increase in serum 1,25(OH)2D2 concentration during 3–4 h haemodialysis sessions, but no other difference in steady-state pharmacokinetics was found between these or hepatically impaired patients and normal subjects.
Conclusions. Given the sensitivity limits of current assays, the pharmacokinetics of this and other vitamin-D compounds is best elucidated from steady-state studies. The pharmacokinetics of 1,25(OH)2D2 from 1(OH)D2 doses appears to be similar to that of 1,25(OH)2D3 from 1(OH)D3 doses, albeit D3 data have to date largely derived from single-dose studies. Deviation of 1,25(OH)2D2 pharmacokinetics from linearity appears to be marginal enough to be clinically manageable with adequate precaution.
Keywords: doxercalciferol; hepatic disease; pharmacokinetics; renal disease; steady state; vitamin D2
Correspondence to: Robert A. Upton, 4-D Minkara Road, Bayview, NSW 2104, Australia. Email: cupton{at}netpro.net.auOffprint requests to: Leon W. LeVan, Bone Care International, 1600 Aspen Commons, Middleton, WI 53562, USA. Email: llevan{at}bonecare.com
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