Cimetidine-induced reduction in gastrointestinal absorption of antipyrine and rate constants for formation of its metabolites.
In 15 normal men, cimetidine taken orally in a dose of 300 mg twice a day for 3 days reduced to similar extents the rate constants for formation (ki) of the three principal metabolites of antipyrine (AP): 29.9% +/- 8.5% (mean +/- SD) for 4-hydroxyantipyrine (4-OH-AP); 28.3% +/- 6.3% for 3-hydroxymethylantipyrine (3-OHM-AP); and 22.4% +/- 5.6% for N-demethylantipyrine (NDM-AP). AP clearance declined 24.3%; AP salivary t 1/2 rose 33%; and corrected AP apparent volume of distribution was unchanged. In one apparently normal subject, however, kis for formation of 3-OHM-AP and NDM-AP rose after cimetidine even though AP clearance declined 19.7%. This surprising result, which suggests that cimetidine can exert an inductive effect on the hepatic mixed-function oxidases of some subjects, was checked by restudying the individual. Very similar values occurred on repetition. The average increase in kis for NDM-AP and 3-OHM-AP was 172.2% and 34.0%. These unusual results in this subject indicate that at least two distinguishable forms of cytochrome P-450 participate in AP metabolism in man. Cimetidine appeared to reduce the amount of AP absorbed from the gut in 10 of our 15 normal subjects.
D000328:Adult; D000983:Antipyrine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000652:urine; D002927:Cimetidine / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D007408:Intestinal Absorption / Q000187:drug effects*; D007700:Kinetics; D008297:Male
C007983:4-hydroxyantipyrine; C031820:3-hydroxymethylantipyrine; C015105:N-demethylantipyrine; D002927:Cimetidine; D000983:Antipyrine