Predictive modelling of the behaviour of a controlled release buflomedil HC1 formulation using scintigraphic and pharmacokinetic data

Abstract A combined scintigraphic and pharmacokinetic study was carried out in seven healthy subjects to evaluate the effect of meal size on the behaviour of an oral controlled release preparation of buflomedil HCl (600 mg). Micronised resin radiolabelled with 111 In was incorporated into the tablets which were administered to subjects after either a light (646 kJ) or a heavy (3327 kJ) breakfast in a randomised cross-over study. The gastrointestinal transit of the formulation, and the buflomedil serum concentrations were monitored for 25 h following administration of the tablets. The mean gastric residence times (± SD) of the formulation after the heavy and light breakfast were 6.2 ± 2.3 and 2.2 ± 0.2 h, respectively ( p μ g ml −1 ) and at 6 h following the heavy meal (2.16 ± 1.0 μ g ml −1 ). The area under the serum-concentration time curve was 21.7 ± 8.1 μ g ml −1 h for the light meal and 24.8 ± 10.5 μ g ml −1 h for the heavy meal. The transit data and the in vivo release rates of the radioactive marker from the tablet were used in a computer simulation to demonstrate that the observed serum concentrations could result from predominantly small intestinal absorption of the drug with a smaller contribution from colonic absorption.