Effects of cimetidine on pharmacokinetics and pharmacodynamics of losartan, an AT1-selective non-peptide angiotensin II receptor antagonist.
This was a 2-period randomized, crossover study in 8 healthy males to determine the effects of cimetidine (400 mg q.i.d. for 6 days) on the pharmacokinetics and pharmacodynamic effects of the angiotensin II receptor antagonist, losartan (100 mg). Cimetidine increased the AUC for losartan 18% without affecting the AUC for E-3174, the active metabolite of losartan. The increase in plasma renin activity following losartan was not affected by cimetidine (maximum mean increases 12.6 and 12.1 ng Ang I.ml-1.h-1 without and with cimetidine, respectively). These results indicate that cimetidine does not appear to alter the pharmacokinetics or pharmacodynamics of losartan to a clinically significant extent.
Goldberg
M R
MR
Merck Research Laboratories West Point, Pennsylvania 19486, USA.
Lo
M W
MW
Bradstreet
T E
TE
Ritter
M A
MA
Höglund
P
P
D000328:Adult; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D002927:Cimetidine / Q000494:pharmacology*; D018592:Cross-Over Studies; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019808:Losartan; D008297:Male; D013777:Tetrazoles / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics* / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D013777:Tetrazoles; D002927:Cimetidine; C066026:losartan carboxylic acid; D019808:Losartan