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KMID : 0043319940170020124
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Archives of Pharmacal Research
1994 Volume.17 No. 2 p.124 ~ p.130
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Nonlinear Renal Excretion of Theophyline and its Metabolites, 1-Methyluric Acid and 1,3-Dimethyluric Acid, in Rats
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Kuhkang Hyo-Jeong
Shim Chang-Koo
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Abstract
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Plasma phamacokinetics and renal excretion of theophylline (TP) and its metabolities were ivnestigated in rats. Plasma concentrations of TP declined in a monoexponential manner, while those of 1-methyluric (MU) and 1,3-dimethyluric(DMU) declined in a biexponential manner upon respective iv bolus injection of each compound at 6mg/kg dose. The total body clearances of the metabolites were 4-6 fold larger than that of TP, while the distribution volumes of them at steady-state were 40-50% smaller than that of TP. The metabolites showed their plasma peaks in 30 min after iv injection of TP indicating than that to MU. Renal excretion of TP and its metabolites was studied in urine flow rate (UFR)-controlled rats. The renal clearance of TP was inversely related to pasma TP concentrations, and much smaller than the glomerular filtration rate (GFR) suggesting tubular secretion and profound reabsorption in the renal tubule. The of each metabolite also showed that inverse relationship, but far exceeded GFR suggesting that tubular secretion than GFR by ip injection of probenecid (142.7 mg/kg). It supports that the metabolies are secreted in the renal tubule, and suggests that they share a common transport system in their sectrtion processes with probenecid. On the other hand, the of TP was not affected significantly by the probenecid treatment. Considering the inverse relationship of TP between the and its ploasma concentrations,no effect of probenecid on of TP is most likely due to negligible contribution of the secretion to the overall of TP.
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KEYWORD
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Theophylline, 1-Methyluric acid, 1, 3-Dimethyluric acid, Renal excretion, Secretion, Reabsorption, Nonlinearity, Pharmacokinetics
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