A primed-infusion technique for rapid estimation of the metabolic clearance rate of 1,25(OH)₂D₃

We have developed a rapid primed-infusion technique for the measurement of the metabolic clearance and production rate of 1,25-dihydroxyvitamin D₃ in normal human subjects and experimental animals. With this method, an estimate of the metabolic clearance rate of 1,25-dihydroxyvitamin D₃ can generally be made within 3 to 4 h. Initial studies in five dogs using 1,25-[³H]-dihydroxyvitamin D₃ (180 Ci/mmol) allowed us to determine the optimal ratio of loading dose to infusion rate that resulted in the most rapid attainment of steady-state levels of plasma radioactivity. By use of this technique we found that the metabolic clearance rate of 1,25-dihydroxyvitamin D₃ in dogs was 6.3 ± 1.2 ml/min (mean ± SD); the production rate of the hormone was 0.40 ± 0.25 μg/day (20.4 ± 14.4 ng· kg^-1·day^-1). In eight normal women, aged 28-51 yr, the metabolic clearance rate for 1,25-dihydroxyvitamin D₃ was 25.9 ± 4.7 ml/min; the production rate was 1.38 ± 0.45 μg/day (20.7 ng·kg^-1·day^-1). The advantages of this method relative to ones used in the past are that it can be performed quickly (generally within 3-4 h) with the use of only tracer amounts of this hormone (equivalent to 1.1% of the production rate). With this method, no assumptions about the most appropriate model to which to fit the data need to be made. Because of its rapidity, no metabolites of the injected 1,25-dihydroxyvitamin D₃ are formed during the study interval.