367 6β-HYDROXYCORTISOL: A NON-INVASIVE PROBE TO EVALUATE INHIBITORY EFFECTS OF LEAD (Pb) ON DRUG METABOLISM IN CHILDREN

Abstract

6β-hydroxycortisol (6βOHF), a normally occurring polar metabolite of cortisol has been shown to be a sensitive index for hepatic enzyme induction. 6βOHF is formed by the mixed function oxidase system in the liver and excreted by the kidney. Pb is known to inhibit hepatic microsomal activity. In order to measure inhibitory effects of lead on drug metabolizing enzyme activity 6βOHF excretion was measured in 11 children (age 2-9 yrs) with mild to moderate Pb intoxication (n1 renal function) prior to chelation therapy. Correlations were examined between 6βOHF and blood Pb, erythrocyte protoporphyrin (EP) and urinary Pb excretion (after a CaNa2EDTA provocative test). 6βOHF excretion in normal controls was 0.23±.03 mg/m2/24h, but excretion in Pb burdened children was reduced to 0.17 ± 2 mg/m2/24h; (p 0.2). The correlation between 17-hydroxycorticoid excretion and EP or urinary Pb was not significant. Conclusions: 1) The data show that children with undue Pb absorption may have decreased 6βOHF excretion; 2) 6βOHF may thus serve as a non-invasive probe to assess the chelatable, potentially toxic, fraction of body Pb stores; 3) 6βOHF may also be used as a non-invasive index to evaluate the inhibitory effects of undue Pb absorption on drug metabolizing enzyme activity.