Cimetidine--acetaminophen interaction in humans.

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 micrograms/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.