Kinetic analysis of 25-hydroxyvitamin D3 metabolism in strontium-induced rickets in the chick.
Kinetic data analysis was used to derive a six-compartment computer model which describes the in vivo [3H]25-hydroxyvitamin D3 ([3H]25-OHD3) metabolism in control and strontium rachitic chicks. Plasma concentrations of 25-OHD3 (13 pmol/ml) and 25, 25-dihydroxyvitamin D3 (0.9 pmol/ml) were 18 and 125% greater than controls, respectively, whereas the corresponding level for 1alpha,25-dihydroxyvitamin D3 (0.3 pmol/ml) was only 30% of control. Plasma disappearance of 25-HOD3 was fitted using a two-compartment model in which the metabolite extrapolated half-life was nearly twice as large for strontium rachitic chicks (71 compared to 41 h). Intestinal sequestration of 1alpha,25-dihydroxyvitamin D3 was assumed to be irreversible and was fitted by a single exponential term in which metabolite uptake rate and tissue concentration in strontium rickets was suppressed to 20 and 10% of control, respectively. In contrast, uptake of 25-OHD3 by the intestine was observed to occur by a reversible process in which metabolite concentration was 45% greater in the strontium rachitic compared to control group. The developed compartment model accepts time-dependent control or perturbed metabolite data for the plasma and (or) intestinal pools and provides quantitative values for metabolite pool size, flux rate, and turnover time.
D000818:Animals; D002645:Chickens; D004032:Diet; D004100:Dihydroxycholecalciferols / Q000097:blood / Q000378:metabolism; D006207:Half-Life; D006887:Hydroxycholecalciferols / Q000097:blood / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008954:Models, Biological; D012279:Rickets / Q000139:chemically induced / Q000378:metabolism*; D013324:Strontium / Q000008:administration & dosage / Q000494:pharmacology*; D014316:Tritium
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D014316:Tritium; D013324:Strontium