Famotidine, a new H2-receptor antagonist, does not affect hepatic elimination of diazepam or tubular secretion of procainamide.
In 8 healthy male volunteers the pharmacodynamic responses to a single dose of diazepam and a single dose of procainamide were assessed before and after pre-treatment with the H2-receptor antagonist famotidine in a randomized crossover study. The pharmacokinetics of diazepam and procainamide were also studied, and the binding of famotidine to human liver microsomes was also measured. Cimetidine induced binding changes with a spectral dissociation constant (Ks) of 0.87 mM, whereas famotidine produced no measurable spectral alteration in concentrations up to 4 mM. The elimination half-life (t1/2: 45.6 h) and total plasma clearance (CL: 0.28 ml/min/kg) of diazepam were not significantly altered by famotidine (t1/2 = 39.0 +/- 11.4 h; CL = 0.31 +/- 0.08 ml/min/kg). Similarly, there was no enhancement of the sedative effect of diazepam by famotidine. The pharmacodynamics and pharmacokinetics of procainamide and N-acetylprocainamide (NAPA), too, were not significantly changed by famotidine: procainamide t1/2 2.9 vs 3.0 h under famotidine and renal clearance (CLR) 436 vs 443 ml/min; and NAPA CLR 195 vs 212 ml/min under famotidine. The data suggest that famotidine, in contrast to cimetidine, does not affect the pharmacokinetics of diazepam (hepatic elimination) or procainamide (tubular secretion). This new H2-receptor antagonist appears to be devoid of an interaction potential for either type of drug elimination.
Klotz
U
U
Arvela
P
P
Rosenkranz
B
B
D000328:Adult; D002927:Cimetidine / Q000378:metabolism; D003975:Diazepam / Q000378:metabolism*; D015738:Famotidine; D006635:Histamine H2 Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D011342:Procainamide / Q000378:metabolism*; D011897:Random Allocation; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D013844:Thiazoles; D015738:Famotidine; D002927:Cimetidine; D011342:Procainamide; D003975:Diazepam