H2 receptor antagonist — first H2 blocker to market; suppresses gastric acid via H2 → cAMP → parietal cell. Inhibits CYP1A2, CYP2D6, CYP3A4, CYP2C9 — substantially raises levels of theophylline, warfarin, phenytoin, propranolol. Largely supplanted by famotidine (no CYP DDI).
Half-Life (t½)
PO: 2h, IV: 2h
Dosing Guidelines
PO: Typical 400 mg (Range: 200–800 mg)
Target Organ Systems
digestive
Interactions
Theophylline (caution): CYP1A2 inhibition. Powell 1984 (PMID:6322709) verbatim: "Cimetidine, 1,200 mg/day, significantly decreased theophylline clearance by 36% (range, 22% to 49%)". 12 healthy men, IV 6 mg/kg aminophylline, 4 arms (control / cim 1200 / cim 2400 / ranitidine 300). CL ↓36% → AUC ratio 1/(1-0.36) = 1.56×. Ki ≈ 5/0.56 = 8.93 µM. t½ 5.7 → 9.2 h. Ranitidine not affected (specificity).
Propranolol (caution): CYP1A2 + CYP2D6 (first-pass) inhibition. Heagerty 1981 (PMID:6786672) verbatim: "The mean increase in bioavailability was 136.5 +/- 57.6%". 6 patients, single 80 mg PO propranolol ± cimetidine. Bioavailability ↑136.5% → AUC ratio 2.37×. Ki ≈ 5/1.37 = 3.66 µM. "Cimetidine reduces the hepatic first-pass extraction of propranolol."
Diazepam (caution): CYP2C19 + CYP3A4 inhibition. Pasanen 1986 (PMID:2878667) verbatim: "in man, only C inhibited the hepatic elimination of diazepam by about 45%" (comparing 5 H2-antagonists; only cimetidine [C] inhibited). CL ↓45% → AUC ratio 1/(1-0.45) = 1.82×. Ki ≈ 5/0.82 = 6.10 µM. Specificity vs ranitidine/famotidine/etc confirmed in same study.
Warfarin (caution): CYP2C9 inhibition. Kirch 1984 review (PMID:6096071) verbatim: "warfarin clearance was significantly reduced from 66.7 to 48.7 ml/min by ranitidine, and by cimetidine to 42.9 ml/min". CL ratio 66.7/42.9 = 1.555 → AUC ratio 1.55×. Ki ≈ 5/0.55 = 9.01 µM. Caveat: secondary reporting in a review paper (Kirch); primary source is Serlin/Toon era 1980-83 studies.