Production and metabolic clearance rates of 1,25-dihydroxyvitamin D3 during maturation in rats: studies using a rapid, primed-infusion technique.
I have adapted the primed-infusion technique for the rapid estimation of the metabolic clearance rate (MCR) and production rate (PR) of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in chronically catheterized conscious rats. Following a bolus injection, [3H]-1,25(OH)2D3 was infused iv at a constant rate for 7 h. Steady-state [3H]-1,25(OH)2D3 levels in plasma were achieved within 3 h. HPLC-purification of plasma [3H]-1,25(OH)2D3 was necessary. This rapid, primed-infusion technique thus eliminates the need for protracted infusions to achieve steady-state plasma [3H]-1,25(OH)2D3 levels. The MCR averaged 0.201 +/- 0.003 ml.min-1.kg-1 in fed male rats weighing 200-300 g. This MCR is approximately 50% lower than that seen in other species. Overnight fasting was without effect on the MCR. The MCR increased in direct proportion to body weight in maturing rats (6-16 weeks old) weighing 150-450 g. Thus, the MCR can be normalized per kg across this age range. However, 1,25(OH)2D3 production and plasma levels both decreased by 65-67% as the rats matured. The failure of a 3-fold decrease in plasma 1,25(OH)2D3 levels to affect the MCR suggests that 1,25(OH)2D3 stimulates its own catabolism only at markedly elevated concentrations.
Fox
J
J
Department of Physiology, Tulane University School of Medicine, New Orleans, Louisiana.
D000818:Animals; D001835:Body Weight; D002117:Calcitriol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains / Q000254:growth & development*
D002117:Calcitriol