Comparative steady state study with 2 fenofibrate 250 mg slow release capsules. An example of bioequivalence assessment with a highly variable drug.

Abstract Twenty healthy male volunteers were treated with 2 different oral preparations of fenofibrate according to a randomized 2-way crossover design. The test preparation was Fenofibrate 250 mg retard capsules, batch No. YXF 001, provided by MTT Medical and Technological Transfer GmbH, Unterhaching, Germany. The reference preparation was Lipanthyl 250 mg retard capsules, batch No. R9110071, manufactured by Fournier Pharma, Sulzbach, Germany. On 12 consecutive days divided in 2 periods the volunteers received 6 doses of the test and reference formulation, respectively. The daily dose of 1 capsule contained 250 mg of fenofibrate and was administered together with a standardized high calory breakfast. Blood samples were taken immediately prior to each administration and at 14 points after the last administration of each period. The concentration of the pharmacologically active compound, fenofibric acid, was determined by means of HPLC with UV detection. The calibration curve was linear in the range 0.1-20.0 micrograms/ml (r = 0.99997). A lower limit of quantification of 0.1 microgram/ml was established. The following mean values were obtained after administration of the test preparation: AUC tau 184.68 microgramsh/ml; Cmax 13.11 micrograms/ml; PTF: 125.0%. After administration of the reference formulation the following values were observed: AUC tau 175.91 microgramsh/ml, Cmax 12.27 micrograms/ml, PTF: 120.0%. AUC tau, Cmax and PTF were tested for bioequivalence parametrically after logarithmic transformation. The preparations were found to be bioequivalent.