Comparative Review of the Pharmacokinetics of Vitamin D Analogues

Abstract

This article reviews the pharmacokinetic characteristics of calcitriol, paricalcitol, and doxercalciferol, and provides an overview of the metabolism of vitamin D. Calcitriol and paricalcitol have similar pharmacokinetic profiles, with terminal half-lives ranging from 5 to 10 hours in healthy subjects to 15-30 hours in patients undergoing dialysis. Both are active on intravenous administration and little of the active agent remains in the circulation after 24 hours, although they are normally given every 48-72 hours. Doxercalciferol is a prohormone, requiring hepatic metabolism to the active metabolite 1alpha,25-(OH)2D2. The half-life of 1alpha,25-(OH)2D2 is about 34 hours in healthy subjects and about 45 hours in dialysis patients, resembling physiologic blood concentrations of endogenous vitamin D. More studies are warranted to determine the disposition of the vitamin D analogues, especially in selected populations such as pediatric and geriatric dialysis patients.

Up-Regulation of Transporters and Enzymes by the Vitamin D Receptor Ligands, 1α,25-Dihydroxyvitamin D3and Vitamin D Analogs, in the Caco-2 Cell Monolayer

“…Normally, 1,25(OH) 2 D 3 exists at low levels in blood after vitamin D intake (DeLuca, 1988). However, upon administration of the commercially available 1,25(OH) 2 D 3 via injection (calcitriol injection, Calcijex) or capsule (calcitriol, Rocaltrol) for the treatment of hypocalcemia, osteoporosis, hypoparathyroidism, hypoparathyroidism, osteomalacia, rickets, renal osteodystrophy (Bailie and Johnson, 2002), or cancer (Beer and Myrthue, 2006), high systemic levels of 1,25(OH) 2 D 3 are attained. Consequently, due to the marked toxicity associated with 1,25(OH) 2 D 3 , vitamin D analogs that possess less hypercalcemic effects and toxicity are being developed as new drug entities (Masuda and Jones, 2006).…”

Vitamin D Analogs Modulate the Expression of Plasminogen Activator Inhibitor-1, Thrombospondin-1 and Thrombomodulin in Human Aortic Smooth Muscle Cells

“…In healthy individuals, the average level of calcitriol is approximately 45 pg/ml (equivalent to about 0.1 n M ), while the precursor, 25(OH)D 3 , is at 29.6 ng/ml (about 74 n M ) [35]. Calcitriol suppresses the expression of parathyroid hormone with 50% inhibitory concentration in the sub-n M range [36], which is consistent with its endocrine function in mineral homeostatsis and bone metabolism.…”

The Effect of Hepatic Insufficiency on the Safety and Pharmacokinetics of Paricalcitol (Zemplar^®)

“…Preclinical in vitro and in vivo studies demonstrated that paricalcitol has parathyroid hormone-suppressive activity similar to calcitriol (Calcijex TM ; 1α,25-dihydroxyvitamin D 3 ), but has less of an effect on serum calcium and phosphorus concentrations [1]. Paricalcitol pharmacokinetics have been investigated in healthy subjects and in subjects with chronic kidney disease [2]. Following intravenous administration, paricalcitol concentrations decrease rapidly during the first 2 h after a dose; thereafter, paricalcitol concentrations decline log-linearly with a half-life of about 7 h in healthy subjects and about 14 h in subjects with chronic kidney disease [2, 3].…”

“…Paricalcitol pharmacokinetics have been investigated in healthy subjects and in subjects with chronic kidney disease [2]. Following intravenous administration, paricalcitol concentrations decrease rapidly during the first 2 h after a dose; thereafter, paricalcitol concentrations decline log-linearly with a half-life of about 7 h in healthy subjects and about 14 h in subjects with chronic kidney disease [2, 3]. Other results in healthy subjects suggest that paricalcitol is extensively metabolized and is eliminated primarily by hepatobiliary excretion [3].…”