Human Pharmacokinetics and Comparative Bioavailability of Loperamide Hydrochloride

Abstract

A pharmacokinetic study of the antidiarrheal agent loperamide hydrochloride (Imodium) was conducted in 6 male subjects. A random crossover design and a 2 mg capsule and a 0.2 mg/ml syrup formulation was utilized. Each treatment consisted of a single oral dose of 8 mg loperamide HCl followed by a 2 wk interval before the next treatment. Serum and urine samples obtained at various times after drug administration were assayed for loperamide using a radioimmunoassay specific for the drug. The mean biologic half-life, calculated from the elimination phase of the log serum concentration vs. time data, was 10.8 .+-. 0.6 h for the overall study, 10.2 .+-. 0.6 h for the syrup formulation and 11.2 .+-. 0.8 h for the capsules. The loperamide from the syrup was absorbed more rapidly than from the capsule formulation, with the peak serum levels observed at a mean time of 2.4 .+-. 0.7 h for the syrup and 5.2 .+-. 0.3 h for the capsule formulation. The relative areas under the serum loperamide concentration vs. time curves suggested that the 2 formulations have comparable physiologic availability. The maximum observed serum concentrations were also similar, indicating the safety of the syrup formulation. Excretion of approximately 1% of the dose in the urine as unchanged loperamide after 7 days was observed independent of the particular dosage form that was administered.