[Biological availability of gastric juice-resistant coated diclofenac preparations. 1. Bioavailability study following a single administration of a multiple-unit formulation in comparison with a single-unit formulation].

Bioavailability Study of Enteric Coated Diclofenac Formulations/1st Communication: Bioavailability study following single-dose administration of a multiple-unit formulation compared with a single-unit formulation Relative bioavailability of diclofenac (CAS 15307-86-5) was investigated after single-dose administration of an enteric coated multiple-unit formulation (Diclo-Puren 50, test) in comparison to a single-unit dosage form (reference). The study was carried out in a three-way changeover design with a group of 18 healthy male volunteers. Diclofenac plasma concentrations were measured using a selective and sensitive GLC-MS method after liquid-liquid extraction and subsequent derivatisation. Area under the curve (AUC) and maximum plasma concentrations (Cmax) were evaluated as pharmacokinetic characteristics. Moreover, time of maximum plasma concentration (tmax), lag-time (tlag) and plateau time of concentrations above minimum effective concentrations (MEC) of 50 ng/ml (tMEC(50)) and 100 ng/ml (tMEC(100)), respectively were calculated. Bioequivalence concerning AUC and Cmax was assessed by calculating 90%-confidence intervals using parametric (ANOVA, ANOVAlog) and non-parametric (Mann-Whitney) methods. Due to the inclusion rule bioequivalence was accepted if one of the calculated intervals was completely in the range of 80 to 125% (AUC) and 70 to 143% (Cmax). tmax, tlag and tMEC were evaluated considering the differences of mean values. Individual plasma profiles of diclofenac are more homogeneous after administration of the test formulation than after administration of the reference product. Mean relative bioavailability of the test formulation was calculated as 99%. Maximum plasma concentrations (mean +/- SD) were determined as 1159 +/- 632 ng/ml (test) and as 1481 +/- 637 ng/ml (reference). Maximum plasma concentrations (mean +/- SD) occurred 1.4 +/- 0.7 h (test) and 1.8 +/- 0.7 h (reference) after administration.(ABSTRACT TRUNCATED AT 250 WORDS)