Journal Article

Pharmacokinetics of doxercalciferol, a new vitamin D analogue that lowers parathyroid hormone

Robert A. Upton, Joyce C. Knutson, Charles W. Bishop and Leon W. LeVan

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 18, issue 4, pages 750-758
Published in print April 2003 | ISSN: 0931-0509
Published online April 2003 | e-ISSN: 1460-2385 | DOI:
Pharmacokinetics of doxercalciferol, a new vitamin D analogue that lowers parathyroid hormone

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Background. This is the first detailed pharmacokinetic report published on the administration of doxercalciferol [1α(OH)D2] recently introduced to treat secondary hyperparathyroidism.

Methods. 1α(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 1α(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 1α(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 1α(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 1α(OH)D2 doses appears to be similar to that of 1,25(OH)2D3 from 1α(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

Journal Article.  6875 words.  Illustrated.

Subjects: Nephrology

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