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Salicylate metabolite kinetics after several salicylates
Author(s) -
Bochner Felix,
Graham Garry G,
Cham B Elliot,
Imhoff Debra M,
Haavisto Teresa M
Publication year - 1981
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1981.158
Subject(s) - salicylic acid , chemistry , gentisic acid , sodium salicylate , metabolite , urine , aspirin , pharmacokinetics , chromatography , elimination rate constant , sodium , kinetics , pharmacology , biochemistry , medicine , organic chemistry , volume of distribution , physics , quantum mechanics
Single oral doses of aspirin (ASA, 1,500 mg), sodium salicylate (NaSA, 1,500 mg, 1,200 mg), and salicyluric acid (SUA, 500 mg) were given to five subjects. Serial plasma and urine samples were collected for 24 hr (plasma) and up to 48 hr (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 CP SUA = A‐Bt‐Ce −αt − (A‐C)e −βt . Michaelis constants (Vm and Km) for the conversion of SA to SUA were calculated from the equation , where Cl is the renal clearance of SUA, k e is the rate constant of elimination of SUA, Cp SA is the plasma concentration of salicylic acid. The term is the estimated rate of formation of SUA from SA at any time (t). The calculated values (mean ± SD) of Vm, Km, and Km f (Km in terms of unbound SA) were 43.4 ± 10.1 mg SA/hr, 14.3 ± 3.4 mg SA/l plasma, and 0.75 ± 0.15 mg unbound SA/l plasma. The Vm 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. Clinical Pharmacology and Therapeutics (1981) 30, 266–275; doi: 10.1038/clpt.1981.158