Human cytochrome P450 maximal activities in pediatric versus adult liver

Drug clearance is often higher in children than in adults, particularly whe n normalized to body weight. We previously showed that liver volume normali zed to body weight was inversely related to age, but that the systemic clea rance of a nonspecific cytochrome P450 (CYP) substrate (antipyrine) was hig her in young children compared with adults even when normalized per liver v olume. Our purpose herein was to evaluate whether P450 catalytic activities , expressed as maximal catalytic rates per milligram of microsomal protein, differed in up to 37 normal livers from subjects <10 (range 0.5-9 years of age), >10 but <60 years of age (range 10-59 years), and >60 year (range 63 -93 years of age). There were no age-related differences in the oxidation o f ethoxyresorufin (P = .83) (CYP1A2), ethoxycoumarin (P = .52) (CYP2E1 and other P450s), teniposide (P = .58), midazolam (P = .47) (CYP3A4/3A5), or pa clitaxel (P = .24) (at the 17 alpha position, CYP2C8). Tolbutamide hydroxyl ation tended to be lower in children versus adults (P = .047) (CYP2C9), but did not reach statistical significance after correcting for multiple compa risons. No relationship was found to exist between age and microsomal recov ery (P = .98); thus, recovery did not account for the lack of age-related d ifferences in catalytic activity. We conclude that increased intrinsic cyto chrome P450 activity is unlikely to account for increased clearance of most P450 drug substrates in children.