Bioequivalence evaluation of two different oral formulations of loperamide (Diarex Lactab vs Imodium capsules).

Twenty-four healthy male volunteers were treated with two different oral formulations of loperamide according to a randomized two-way cross-over design. The test preparation was Diarex Lactab (Mepha), the reference preparation Imodium 2 mg capsules. Divided in two periods the volunteers received single 8 x 2 mg (= 16mg) doses of the test and reference formulation, respectively. Blood samples were taken immediately prior to each administration and at 14 points within 60 h after the dose. A wash-out period of 1 week was interpaused between successive drug doses. The plasma concentration of the pharmacologically active compound, loperamide, was determined by HPLC with electrochemical detection. The calibration function was linear in the range 0-10.0 ng/ml. A lower limit of quantification of 0.2 ng/ml was established. The pharmacokinetic parameters Cmax and tmax were obtained directly from plasma data. The elimination constant was estimated by log-linear regression of the measured concentrations in the terminal phase. AUC was calculated by the trapezoidal rule and extrapolated to infinity. The following mean values were obtained after intake of 16 mg loperamide as film coated tablets: AUC0 infinity 62.04 ngh/ml, Cmax 3.35 ng/ml, tmax 4.08 h, t1/2 19.66 h and after administration of the capsules: AUC0 infinity 66.56 ngh/ml, Cmax 3.98 ng/ml, tmax 4.38 h, t1/2 18.43 h. The pharmacokinetic parameters AUC0 infinity and Cmax were tested for bioequivalence parametrically (two one-sided t-tests) after logarithmic transformation of data. Differences of tmax were evaluated non-parametrically. The preparations were found to be bioequivalent and, therefore, interchangeable.

RCT Entities:   Population Interventions Outcomes