PHARMACOKINETIC ANALYSIS OF THE ABSORPTION CHARACTERISTICS OF DICLOFENAC SODIUM IN MAN BY USE OF A MULTI-SEGMENT ABSORPTION-MODEL

The pharmacokinetic analysis of an oral sustained-release preparation of diclofenac sodium has been investigated using multi-segment absorpt ion models in which it has been assumed that the gastrointestinal trac t can be divided into several segments in each of which the drug has i ts own lag-time and absorption rate constants. Plasma concentration-ti me data for sustained release diclofenac sodium in man were fitted bot h by a conventional pharmacokinetic method assuming first-order absorp tion and by a multi-segment absorption model. The plasma concentration of diclofenac sodium calculated on the basis of the multi-segment abs orption model was found to correlate with the observed plasma concentr ation. It was concluded that diclofenac sodium data can be better desc ribed by a multi-segment absorption model than by a conventional pharm acokinetic model. The results also show that multi-segment absorption models are suitable for pharmacokinetic analysis of plasma drug-concen tration data with irregular or multiple peaks in the absorption profil es, and also for the pharmacokinetic analysis of sustained-release pre parations.