A comparison of gastrointestinal permeability induced by diclofenac-phospholipid complex with diclofenac acid and its sodium salt.

PURPOSE Gastrointestinal (GI) side effects of the nonsteroidal anti-inflammatory drug (NSAID) diclofenac may be reduced if it is administered as a complex with phospholipid. The upper and lower GI permeability induced by a diclofenac-dipalmitoyl phosphatidyl choline (DPPC) complex were compared with those of diclofenac acid and its sodium salt in rats. METHODS Pharmacokinetic studies were carried out to assess bioavailability of diclofenac preparations. Adult male Sprague-Dawley rats were dosed orally (equivalent to 15 mg/kg diclofenac sodium) as the acid or its sodium salt as well as diclofenac-DPPC complex. Upper and lower GI permeability, as surrogate markers of toxicity were determined using sucrose and 51Cr-EDTA, respectively. RESULTS At 1 h post-dose only diclofenac sodium induced a significant increased upper GI permeability. Three h post-dose all formulations significantly increased upper GI permeability although the diclofenac acid had the least effect. In the lower GI tract, the induced increase in permeability was significant at 1 and 3 h post-dose for all formulations with no significant differences between them. CONCLUSION The induced upper and lower GI toxicity of diclofenac was formulation and time dependent. The lack of effect of diclofenac acid was due to the decreased availability of the drug. In the upper GI tract, up to 1 h post-dose, the diclofenac-DPPC complex demonstrated reduced upper gastroduodenal permeability as measured by sucrose. However, the protective effect of DPPC did not last and was not extended to the lower GI tract due to the systemic effect, contribution from the enterohepatic recirculation and/or dissociation of the complex. In assessing diclofenac GI toxicity, the effect of the different formulations on the entire GI tract at various times after drug administration must be considered.