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• W2068005011 abstract "The aim of the study was to develop a physiologically based pharmacokinetic (PBPK) model of rhein to predict human pharmacokinetics before dosing for the first time in human beings. After oral administration of rhein at the doses of 35, 70 and 140 mg/kg in rat, rhein had the following mean plasma pharmacokinetic properties: t1/2 of 3.2, 3.6 and 4.3 hr, AUC∞ of 69.5, 164.3 and 237.8 μg/h/ml and CL/F of 503.4, 426.1 and 588.8 ml/hr/kg, respectively. In vitro, the intrinsic clearance (Clint ) of rhein in cytochrome P450 (CYP450), UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) metabolism of rat was 0.6, 7.8, and 5.5 μl/min/mg protein, respectively. The Clint of rhein in CYP450, UGT and SULT of human beings was 0.10, 1.36 and 0.68 μl/min/mg protein. The rat pharmacokinetics and the metabolism data in vitro were used to construct the PBPK model of rhein, and the observed plasma drug concentration profiles of rhein in rat were validated by a PBPK model. Subsequently, the plasma drug concentration profiles of human beings by the present PBPK model were validated by experimental data in human beings accurately." @default.
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• W2068005011 date "2013-11-08" @default.
• W2068005011 modified "2023-10-16" @default.
• W2068005011 title "Prediction of Human Pharmacokinetics from Preclinical Information of Rhein, an Antidiabetic Nephropathy Drug, Using a Physiologically Based Pharmacokinetic Model" @default.
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• W2068005011 doi "https://doi.org/10.1111/bcpt.12148" @default.
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