Comparative pharmacodynamics of CYP2B induction by phenobarbital in the male and female F344/NCr rat.
The phenobarbital dose-CYP2B induction response relationships and pharmacodynamics of CYP2B induction have been characterized in female and male F344/NCr rats. The ED50 and EC50 values for the induction, by phenobarbital, of hepatic CYP2B1 or 2B1/2B2 protein or associated catalytic activities (benzyloxy- or pentoxyresorufin O-dealkylation or testosterone 16 beta-hydroxylation) were 2- to 7-fold higher in the female than in the male rat, indicating a somewhat decreased potency for this effect in the female rat. In contrast, the maximal induction, expressed as the ratio of induced activity to control activity, was as great or greater in the female rat than in the male. Thus, any difference in the responsiveness of female rats to hepatic CYP2B induction by phenobarbital, compared to male rats, is reflected in potency but not degree of induction of catalytic activity or immunoreactive protein.
Nims
R W
RW
Chemistry Section, National Cancer Institute, Frederick, MD.
Lubet
R A
RA
Jones
C R
CR
Mellini
D W
DW
Thomas
P E
PE
D000818:Animals; D001835:Body Weight; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009929:Organ Size; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital