Lack of effect of phenobarbital on ex vivo leukocyte oxidative metabolism in healthy volunteers.
Oxidative metabolism in activated human polymorphonuclears catabolizes leukotriene B4 by a cytochrome P450 omega-hydroxylase and procainamide by a myeloperoxidase. The percentage of leukotriene B4 metabolized by activated human polymorphonuclears and the apparent enzymatic parameters of procainamide metabolism were studied ex vivo in six healthy volunteers before and after phenobarbital intake (100 mg/day) for 10 days and in six healthy control volunteers. No differences were found between groups for the difference in percentage of leukotriene B4 metabolized between day 11 and day 1. The apparent enzymatic parameters, Km and Vm, of procainamide oxidation did not differ significantly between the groups both on day 1 and day 11. These results do not show any evidence of inducibility of leukotriene B4 and procainamide metabolism in human polymorphonuclears. However, a positive correlation between 6 beta OH-cortisol excretion and percentage of leukotriene B4 metabolized was observed on day 11. This study suggests that human polymorphonuclears cytochrome P450 leukotriene B4 omega-hydroxylase and procainamide metabolism is not a useful method to study cytochrome P450 induction in clinical pharmacology.
Pinquier
J L
JL
ECLIMED, Institut de Recherche Thérapeutique, Hôpital Cochin, Paris, France.
Joseph
X
X
Delaforge
M
M
Lejus
C
C
Boucher
J L
JL
de Lauture
D
D
Kahan
A
A
Strauch
G
G
D015065:17-Hydroxycorticosteroids / Q000652:urine; D000328:Adult; D015415:Biomarkers; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000097:blood; D004790:Enzyme Induction; D006801:Humans; D006854:Hydrocortisone / Q000031:analogs & derivatives / Q000652:urine; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology*
D015065:17-Hydroxycorticosteroids; D015415:Biomarkers; D007975:Leukotriene B4; C001380:6 beta-hydroxycortisol; D003577:Cytochrome P-450 Enzyme System; D006854:Hydrocortisone; D010634:Phenobarbital