Pharmacokinetics of Diclofenac and Misoprostol When Administered Alone or as a Combination Product

Abstract

The pharmacokinetics of a new diclofenac/misoprostol combination dosage form have been investigated. Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that has been commercially available for many years and its pharmacokinetics are well documented. Similarly, misoprostol is a prostaglandin analogue with well documented pharmacokinetics. It is available commercially as both an effective treatment for peptic ulceration and as prophylaxis of NSAID-induced gastric and duodenal damage. The aim of studies of the diclofenac/misoprostol combination dosage form has been to determine the potential for drug-drug interactions between the 2 drugs when they are coadministered. A single dose crossover study in young healthy volunteers showed no statistically significant differences between the plasma concentrations of either diclofenac or misoprostol when the drugs were each administered alone and those after administration of the combination dosage form. Although not statistically significant, slight variations in plasma diclofenac concentrations appeared to occur between dosage forms. Use of a replicate design study in which the same dosage of diclofenac was administered in 2 different treatment periods to elderly volunteers showed that this variation was due to interindividual variations in the disposition of diclofenac. The latter study had both single and multiple dose components and confirmed the lack of interaction between misoprostol and diclofenac at steady-state. Thus, diclofenac and misoprostol may be given in a combination dosage form without either drug altering the pharmacokinetics of the other.