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Kinetics of Intravenously Administered 25-Hydroxyvitamin D₃ in Sheep and the Effect of Exposure to Ultraviolet Radiation

Agriculture Canada, Ottawa, Canada K1A 0C6

Abstract

This report describes studies of 25-hydroxyvitamin D₃ (250HD₃) kinetics in 10 yearling crossbred wethers (40 to 52 kg body weight) administered [³H] 25-hydroxyvitamin D₃ ([³H] 250HD₃). The wethers were divided into two groups of five before dosing with the labeled compound: Group 1 wethers were exposed 2 h daily for 8 to 10 wk to ultraviolet radiation from fluorescent sunlamps. Plasma 250HD₃ increased from 13 to 31 ng/ml by d 25 and then remained at a steady-state concentration until d 70. In the non-ultraviolet-exposed wethers (Group 2), plasma 250HD₃ averaged 13.2 ng/ml and did not change over the course of the experiment. Six weeks after the start of the experiment three wethers from each group were injected intravenously with 50 µCi of [³ H] 250HD₃, and the other two wethers from each group were similarly dosed 2 wk later. Blood was drawn at suitable time intervals for up to 240 h post-dosing. The kinetic data were satisfied by curve-fitting the data to a two-compartment, pharmacokinetic mathematical model. Individual and mean values for these kinetic analyses are presented with their statistical analyses. Physiological half-life of the tritiated 2500 HD₃ in wethers exposed to ultraviolet irradiation was 388 ± 26.4 h (x ± SE); in the control it was 393 ± 29.6 h (P>.05). In the wethers exposed to ultraviolet the elimination and clearance rates of 250HD₃ were significantly greater than in the control wethers. A two-compartment model provided an acceptable description of 250HD₃ disposition kinetics in wethers. Turnover rate constants did not seem to change, but changes were due to increased pool size in the irradiated wethers.

¹ Contribution no. 1417 Anim. Res. Centre, Ottawa, K1A 0C6.

² The author is grateful to Dr. K. Karpinski, statistician (Food Directorate, Health and Welfare, Ottawa) for his advice and help in the statistical analyses of the data.