ANTIPYRINE CLEARANCE IN CONGENITAL ADRENAL HYPERPLASIA

Antipyrine (AP) metabolism was studied in four adult patients with congenital adrenal hyperplasia (CAH) due to classical 21-hydroxylase deficiency and in four (adult) patients with CAH due to non-classical 21-hydroxylase deficiency. This investigation was prompted by the known biochemical and functional similarities between drug- and steroid-metabolizing enzymes. We hypothesized that a common genetic mechanism may regulate the expression and activity of both the adrenal and hepatic cytochrome P450 enzymes. AP half-lives (T1/2, mean +/- SD) were 10.7 +/- 2.1 h in classical CAH patients, 10.1 +/- 0.4 h in the nonclassical CAH patients and 10.9 +/- 2.2 h in the control group, suggesting that there was no significant difference in AP metabolism among the three groups. Similarly, no significant differences were found in the AP apparent volume of distribution (aVd) and metabolic clearance rate (MCR) among the three groups. These results indicate that despite the deficiency of adrenal cytochrome P450 in patients with 21-hydroxylase deficiency CAH, these individuals have normal hepatic drug metabolizing activity for the biotransformation of AP.