BIOEQUIVALENCE EVALUATION OF 2 DIFFERENT ORAL FORMULATIONS OF LOPERAMIDE (DIAREX-LACTAB VS IMODIUM CAPSULES)

Twenty-four healthy male volunteers were treated with two different or al formulations of loperamide according to a randomized two-way cross- over design. The test preparation was Diarex Lactab (Mepha), the refer ence preparation Imodium 2 mg capsules. Divided in two periods the vol unteers received single 8 x 2 mg (= 16 mg) doses of the test and refer ence formulation, respectively. Blood samples were taken immediately p rior to each administration and at 14 points within 60 h after the dos e. A wash-out period of 1 week was interpaused between successive drug doses. The plasma concentration of the pharmacologically active compo und, loperamide, was determined by HPLC with electrochemical detection . The calibration function was linear in the range 0 - 10.0 ng/ml. A l ower Limit of quantification of 0.2 ng/ml was established. The pharmac okinetic parameters C-max and t(max) were obtained directly from plasm a data. The elimination constant was estimated by log-linear regressio n of the measured concentrations in the terminal phase. AUC was calcul ated by the trapezoidal rule and extrapolated to infinity. The followi ng mean values were obtained after intake of 16 mg loperamide as film coated tablets: AUC(0-infinity) 62.04 ngh/ml, C-max 3.35 ng/ml, t(max) 4.08 h, t(1/2) 19.66 h and after administration of the capsules: AUC( 0-infinity) 66.56 ngh/ml, C-max 3.98 ng/ml, t(max) 4.3 8 h, t(1/2) 18. 43 h. The pharmacokinetic parameters AUC(0-infinity) and C-max were te sted for bioequivalence parametrically (two one-sided t-tests) after l ogarithmic transformation of data Differences of t(max) were evaluated non-parametrically, The preparations were found to be bioequivalent a nd, therefore, interchangeable.