Prediction of Pharmacokinetics and Penetration of Moxifloxacin in Human with Intra-Abdominal Infection Based on Extrapolated PBPK Model

다국어 초록 (Multilingual Abstract)

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intraabdominalinfected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profilesin various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections,induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Bloodplasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK modelwas developed in rats and extrapolated to human using GastroPlus software. The predictions wereassessed by comparing predictions and observations. In the plasma concentration versus time profileof moxifloxcinin rats, Cmax was 11.151 μg/mL at 5 min after the intravenous injection and t1/2 was2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas.
Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart,liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue toplasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrationswere known, extrapolation of a PBPK model was a method to predict drug pharmacokineticsand penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well asother tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacindue to its high concentration distribution. This pathological model extrapolation may provide referenceto the PK/PD study of antibacterial agents.

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