Cimetidine—Acetaminophen Interaction in Humans

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Abstract
The effect of single‐dose and multiple‐dose cimetidine administration on acetaminophen pharmacokinetics was investigated in a three‐phase, randomized, crossover study using four normal subjects. In each phase of the study, subjects ingested 750 mg of acetaminophen as a single dose alone (A), or in combination with 200 mg of cimetidine (A + C), or following a one‐week pretreatment with daily cimetidine, 200 mg every six hours and 400 mg before retiring (A + C*). Statistical analysis using two‐way analysis of variance indicated no significant difference in peak concentration and peak time of acetaminophen between treatments. Cimetidine did not significantly affect acetaminophen half‐life, 2.38 hours (A), 2.65 hours (A + C), and 2.50 hours (A + C*). Acetaminophen clearance was minimally affected by cimetidine; the mean clearance of acetaminophen ranged from 4.16 (A + C*) to 5.57 mL/min/kg (A). Area under the acetaminophen plasma concentration‐time curve was slightly increased by cimetidine, 35.4 (A), 41.6 (A + C), and 47.6 μg/mL/h (A + C*). Since cimetidine did not affect acetaminophen pharmacokinetics to any significant extent, clinical combination of both medications at therapeutic dosage presumably would not produce adverse interactions.