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KMID : 0043320030260110979
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Archives of Pharmacal Research
2003 Volume.26 No. 11 p.979 ~ p.983
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Pharmacokinetics of Tolbutamide After Oral Administration to Rabbits with Folate-Induced Renal Failure
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Choi Jun-Shik
Shin Sang-Chul
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Abstract
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The pharmacokinetic of tolbutamide was studied after the oral administration to normal rabbits or rabbits with mild to medium folate-induced renal failure. The plasma concentrations of tolbutamide were significantly elevated (p<0.05) during 9 to 24 h in rabbits with mild or medium folate-induced renal failure. Consequently, the area under the plasma concentration-time curves (AUC) was significantly higher in mild (p<0.05) and medium (p<0.01) folate-induced renal failure rabbits (i.e., 2906 g/mLh for mild renal failure and 4074 g/mLh for moderate renal failure) than that in normal rabbits (i.e., 2295 g/mLh). The cumulative urinary excretion of tolbutamide was significantly depressed (p<0.05) in medium folate-induced renal failure rabbits (i.e., 3.3 mg) compared with that in normal rabbits (i.e., 5.9 mg). The elimination rate constant (Kel) of tolbutamide was significantly decreased in medium renal failure rabbits (i.e., 0.027 ) than that in normal rabbits (i.e., 0.044 ); As a result, the terminal half-life of tolbutamide in medium folate-induced renal failure rabbits (i.e., 25.5 h) was significantly longer (p<0.01) than that in normal rabbits (i.e., 15.7 h). The change in pharmacokinetic parameters is consistent with the hypothesis that the alteration is mediated by the depressed metabolic elimination of the drug by the induction of renal failure. Therefore, these observations indicated that the dosage adjustment may be necessary for tolbutamide in patients with renal insufficiency.
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KEYWORD
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Tolbutamide, Pharmacokinetics, Oral admimstration, Renal failure
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