Comparative Pharmacokinetics of Salicylic Acid and Copper Salicylate in Rats

Abstract

The objective of this study was to provide a basic understanding of the effect of complexation with copper on the pharmacokinetics of salicylic acid (SA). Male Sprague-Dawley rats (250–300 gms) received an I.V. dose of either SA or copper-salicylate complex, (Cu-SA) (10 mg/kg of SA) in a randomized balanced crossover fashion. Based on free copper ion measurements, the amount of intact complex in the vehicle used to prepare the drug solution for injection ranged between 68.4 and 76.6%. Serial blood samples (100 ul) were drawn for 12 hours post administration. Plasma samples were analyzed for SA by reversed phase HPLC on a C-18 column with U.V. detection at 237 nm. The SA concentration-time profiles were similar up to the first 90 minutes for both treatments. For the remainder of the sampling period, SA concentrations were consistently lower where the animals had received Cu-SA. In rats (n=5) injected with Cu-SA, SA declined monoexponentially with an elimination rate constant (mean ± SD) of 0.0108 ± 0.00146 min^-1, a plasma clearance of 2.15 ± 0.621 ml/(min kg) and a Vd of 188.2 ± 38.67 ml/kg. In contrast, rats injected with SA showed a biexponential decline of the drug with a 3 of 0.00475 ± 0.00144 min-1, plasma clearance of 1.08 ± 0.153 ml/(min-kg) and Vd(3) of 243.4 ± 44.96 ml/kg. Non-com-partmental analysis of SA concentration-time data following Cu-SA administration gave Vd(SS) and MRT values of 190.5 ± 31.81 ml/kg and 92.29 ± 9.279 min, respectively. The corresponding values after SA administration were 232.9 ± 40.17 ml/kg and 211.7 ± 73.88 min. Differences in the terminal rate constants, volumes of distribution (Vd(β)), clearances and MRT between the two treatments were significant (p<0.05).