BIOEQUIVALENCE OF 2 ORAL CYCLOSPORINE PREPARATIONS

A comparison of bioequivalence of two cyclosporine (CAS 59865-13-3) pr eparations was performed. Ten cyclosporine treated patients with trans planted kidneys were included. Criteria were successful transplantatio n and minimum period from transplantation of at least 6 months. Two mo nths before the experiment, cyclosporine concentrations had to be in t herapeutic range without significant oscillation, and kidney function stabile. There had to be no signs of cyclosporine nephrotoxicity Durin g the objective biochemical analysis it was not allowed to find malfun ction in any of the patient's ol gcm important for cyclosporine pharma cokinetics. Cyclosporine concentrations in It hole blood were measured with a specific flouroimmunoassay. Cyclosporine and metabolites conce ntrations, were measured with radioimmunoassay with non-specific antib ody. Mean value and standard deviations and shape of distribution were calculated for all numeric data of patients, measured biochemical and other laboratory parameters. Variance analysis for all measured cyclo sporine concentrations according to sampling times (C-0 to C-12, maxim al concentrations C(M), time to maximal concentrations t(M), times of absorption delaying t(Lag) and area under the measured concentration c urves (AUC) were statistically checked. According to these data it is concluded that the preparations are bioequivalent; a time to reach max imum concentration was slightly shorter for rest preparation (2.5 and 3.2 h, respectively), but not statistically significant. There are no significant differences between the areas under the concentration curv es (1667 and 1665 ng . h/ml, respectively). After the calculation of p harmacokinetic parameters of concentration data measured by a non-spec ific method a significant difference for areas under concentration cur ves was seen (3709 and 4600 ng . h/ml, respectively). According to the se data the relative biological availability of the test preparation w as 80 % if the comparison was based on the concentrations measured wit h non-specific analytical method.