Pharmacokinetic analysis of an oral sustained-release diltiazem preparation using multifraction absorption models.

Application of multifraction absorption models to pharmacokinetic analysis of an oral sustained-release diltiazem preparation (HER-SR) was investigated. The plasma diltiazem concentrations after oral administration of the HER-SR preparation were analyzed using both the two-fraction absorption model and the two-step discontinuous absorption model. The two-fraction absorption model was suitable for the pharmacokinetic analysis of the HER-SR preparation, whereas the two-step discontinuous absorption model is often unsuitable for the analysis of sustained-release preparations which disintegrate into fractions with different release characteristics in the gastrointestinal tract. The two-step discontinuous absorption model is usually not applicable to plasma concentration data when the first peak is sharp. MFA-MULTI(V) was shown to be useful for the prediction of the bioavailability in each fraction of HER-SR. It was further demonstrated that a two-fraction absorption model is useful for the comparison of in vitro and in vivo release profiles or evaluating the influence of food on the absorption behavior of HER-SR. In addition, the application of a two-fraction absorption model to population pharmacokinetics of HER-SR was investigated.