Determination of Copper at Extended Dose Levels of Copper (II)-acetylsalicylate and Pharmacokinetics Applications

Abstract

Rheumatoid arthritis has long been treated with acetylsalicylic acid, despite many side effects, including gastric ulcers. These side effects can be curtailed by preparing the metal complexes of8 acetylsalicylic acid, such as copper (II)-acetylsalicylate (CAS). Present study evaluates the pharmacokinetics parameters of CAS and the level of copper at extended dose levels using rabbit model. The concentrations of CAS and copper in plasma samples were determined by validated HPLC and atomic absorption spectroscopic (AAS) methods, respectively. Three doses, 1-3 mg Kg^-1 were orally administered to six rabbits with two wash out periods. The blood samples were collected at different time intervals for 24 hours. The peak drug concentration (C_max) for these doses at a time to peak drug concentration (t_max) 0.5 h was determined to be 0.38, 0.76 and 1.14 µg mL^-1. The half-life of drug (t_1/2) was 8.67, 8.73 and 8.81 h, which are perfect results for once a day dosing. The values of volume of distribution (V_d) and clearance (Cl) for CAS were 829, 833 and 837 L Kg^-1 and 66.30, 66.74 and 66.95 L h^-1, respectively. The AAS results showed that copper levels in rabbit blood plasma were increased with increasing the dosage of CAS, but still remains under the safer limit, which was twofold higher than the reported safe limit.