Salicylate metabolite kinetics after several salicylates

Abstract

Single oral doses of aspirin (ASA, 1500 mg), sodium salicylate (NaSA, 1500 mg, 1200 mg) and salicyluric acid (SUA, 500 mg) were given to 5 [human] subjects. Serial plasma and urine samples were collected for 24 h (plasma) and up to 48 h (urine); salicylic acid (SA), SUA and gentisic acid (GA) were measured by high-pressure liquid chromatography. The plasma concentration/time profiles for SUA after ASA and NaSA were fitted to the empirical equation CpSUA [plasma concentration of SUA] = A-Bt-Ce-.alpha.t - (A-C)e-.beta.t. Michaelis constants (Vmax and Km) for the conversion of SA to SUA were calculated from the equation .**GRAPHIC**. where Cl is the renal clearance of SUA, ke is the rate constant of elimination of SUA, CpSA is the plasma concentration of SA. The term .**GRAPHIC**. is the estimated rate of formation of SUA from SA at any time (t). The calculated values (mean .+-. SD) of Vmax, Km and Kmf (Km in terms of unbound SA) were 43.4 .+-. 10.1 mg SA/h, 14.3 .+-. 3.4 mg SA/l plasma and 0.75 .+-. 0.15 mg unbound SA/l plasma. The Vmax values were in accord with those reported, but the value for Km was considerably lower. Renal clearances of SUA and GA were 340 .+-. 51 and 65 .+-. 10 ml/min.