Cimetidine clearance in the obese

Six subjects with normal weight (mean weight = 62 kg) and six obese subjects (mean weight = 140 kg) were given a single intravenous cimetidine infusion of 600 mg over 10 to 15 minutes. Both groups of subjects had normal serum creatinine levels and were matched with respect to age, desirable body weight, height, renal function, and sex. Compared with subjects of normal weight, obese subjects had higher cimetidine systemic (1147 and 637 ml/min) and renal (808 and 318 ml/min) clearances. Volume of distribution at steady state was of the same order for the two groups (82 and 84 L), but the t 1/2 was shorter in the obese group (1.2 and 1.9 hr). Obese subjects had lower cimetidine sulfoxide serum concentrations and greater cimetidine sulfoxide renal clearance (856 and 509 ml/min). Cimetidine systemic clearance and cimetidine sulfoxide renal clearance values were of the same order in the two groups when normalized by the value of weight raised to the 0.76 and 0.5 powers. Under the assumptions of an average weight of 70 kg and that average serum concentrations produced by cimetidine, 300 mg iv every 6 hours, are appropriate, people with normal renal function and body weight usually receive 48 mg/day/weight0.76. This same dosage in obese individuals with normal serum creatinine values should result in the same average steady-state serum concentrations. In our obese subjects, the mean cimetidine dose would have been approximately 500 mg iv every 6 hours.