AGE AND CYP3A4 AND CYP2A6 ACTIVITIES MARKED BY THE METABOLISM OF LIGNOCAINE AND COUMARIN IN MAN

The effect of age on human liver drug-metabolizing ability was investi gated by using probe drugs, metabolized by specific isozymes in liver, as an index. Formation of monoethylglycinexylide (MEGX) after i.v. in fusion of lignocaine (1 mg/kg), metabolized by CYP3A4, and excretion o f 7-hydroxycoumarin (7-OHC) after oral coumarin (5 mg) administration, hydroxylated by CYP2A6, were investigated in healthy young (< 25 year s) and elderly (> 65 years) women and men (n = 10 in each group). MEGX content in young subjects (men 57.8 +/- 11.3 and women 52.9 +/- 13.1 ng/ml) did not diverge significantly but was reduced in elderly subjec ts (men 43.57 +/- 15.8 and women 29.2 +/- 13.6 ng/ml, p < 0.05 and 0.0 1, respectively). 7-OHC excretion at 2 h averaged 68.1 +/- 13.1 per ce nt (men) and 65.0 +/- 18.3 per cent (women) of the dose given in young subjects and was delayed in elderly persons (men 46.5 +/- 16.3 per ce nt and women 44.8 +/- 18.3 per cent, p < 0.01 and 0.05, respectively). The change in probe drug metabolism was related to age (MEGX, r = -0. 473 (men) and -0.682 (women) and 7-OHC; r = -0.690 (men) and -0.565 (w omen)). MEGX formation was reduced by 0.92 mu g/L per year and 7-OHC e xcretion by 0.85 per cent per year. The results indicate a decrease of CYP3A4 and CYP2A6 metabolic activities with age.