Comparison of suspension composition on the pharmacokinetics of nimesulide in rats.

Abstract

Nimesulide is a non-steroidal anti-inflammatory agent that is widely used in the treatment of inflammatory pain. The drug belongs to the class II of Biopharmaceutical Classification System (low solubility, high permeability) and therefore, absorption of this drug is limited by its dissolution. It has been established that complex formation of insoluble substances with cyclodextrins may increase their oral bioavailability since solubility is improved. In order to provide test this hypothesis, a comparison on the oral pharmacokinetics of two suspensions of nimesulide in rats was carried out. Two groups of 7 rats were employed. One group received an oral dose of 10 mg/kg of a suspension prepared with 0.5% carboxymethylcellulose solution in water, whereas the other group received a commercially available formulation containing the complex of nimesulde-beta cyclodextrins (Eskaflam). Blood samples were obtained at selected times for a period of 12 hours and analyzed by an HPLC method. Pharmacokinetic parameters obtained were as follows: Cmax 1.18 +/- 0.16 and 1.93 +/- 0.12 microg/ml, tmax 5.25 +/- 1.03 and 3.21 +/- 0.91 h and AUC 8.65 +/- 1.19 and 13.74 +/- 0.70 microg hr/ml for carboxy-methylcellulose and Eskaflam, respectively. Values for Cmax and AUC12hr were increased and a reduction of tmax was observed indicating improved absorption of nimesulide in the formulation containing beta-cyclodextrins.