LACK OF EFFECT OF PHENOBARBITAL ON EX-VIVO LEUKOCYTE OXIDATIVE-METABOLISM IN HEALTHY-VOLUNTEERS

Oxydative metabolism in activated human polymorphonuclears catabolizes leukotriene B4 by a cytochrome P450 omega-hydroxylase and procainamid e by a myeloperoxydase. The percentage of leukotriene B4 metabolized b y activated human polymorphonuclears and the apparent enzymatic parame ters of procainamide metabolism were studied ex vivo in six healthy vo lunteers before and after phenobarbital intake (100 mg/day) for 10 day s and in six healthy control volunteers. No differences were found bet ween groups for the difference in percentage of leukotriene B4 metabol ized between day 11 and day 1. The apparent enzymatic parameters, Km a nd Vm, of procainamide oxydation did not differ significantly between the groups both on day 1 and day 11. These results do not show any evi dence of inducibility of leukotriene B4 and procainamide metabolism in human polymorphonuclears. However, a positive correlation between 6be taOH-cortisol excretion and percentage of leukotriene B4 metabolized w as observed on day 11. This study suggests that human polymorphonuclea rs cytochrome P450 leukotriene B4 omega-hydroxylase and procainamide m etabolism is not a useful method to study cytochrome P450 induction in clinical pharmacology.