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Pharmacokinetic evaluation after percutaneous administration of some non steroidal antiinflamatory drug preparations using animal experiments

Ani-Simona Sevastre, Florica Popescu, Anca Berbecaru, O. Croitoru, Mihaela Baniceru
Abstract: Background and purpose The non-steroidal antiinflamatory drugs (NSAIDs) are used as elective medication in the therapy of various inflammatory diseases. Th is treatment ameliorates most of the clinical indices of inflammation, improving the exudative-congestive inflammatory process, without influencing the proliferative processes. They are used for the anti-inflammatory effect in the treatment of skin, joints and genital area located chronic inflammatory diseases. The aim of the study was to determine the plasma concentrations of some of the NSAIDs after single dose percutaneous administration in laboratory animals and to monitor their plasma concentrations within 24 hours. Experimental approach We used: male adult rabbits of 3 kg weight, 5% Diclac gel (HEXAL), Indometacin 4% cream (MARK PHARMACEUTICS), FINNIGAN - SURVEYOR liquid chromatograph (BDS - HYPERSIL C18 250X4,6 column, 5 micrometers particle size). For each NSAID, the experiment was simultaneously conducted on 5 rabbits. 24 hours before the experiment, the rabbits were kept fasting. During the experiment, they received water ad libitum. Each rabbit was weighed before the experiment. 24 hours before applying the investigated pharmaceutical formulas on the skin, the hair was removed on the dorsal area of 50 cm2, using a manual cutting mashine. 24 hours after the epilation, the control samples were collected (3 ml of blood). The collection was conducted from the marginal ear vein under the conditions of asepsie, using single use needles and syringes. 2 g of the NSAID pharmaceutical prepation was applied on a 50 cm2 area. The probes were collected at 1,2,3,6,12 and 24 h after the aplication. Each plasma sample was processed for chromatographic analysis. Samples were then analyzed using a FINNIGAN - SURVEYOR liquid chromatograph. During the procedures, the international rules concerning the experiments on laboratory animals were followed as recommended. Results In the fi rst 12 hours, both Diclofenac and Indometacin had a similar progressive increasing of the plasma concentration, which then gradually decreased and maintained up to 24 hours after the percutaneous appliacation. Conclusions and implications Our results support the idea that the topical administered diclofenac and indometacin achieved plasma levels similar to the oral administration plasma levels, but later. The systemic absorption of the topical applied substances emphasizes the possibility of appearance of the corresponding side effects.

Keywords: NSAIDs, diclofenac, indometacin, percutaneous absorption


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