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

The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intraabdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in 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. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, Cmax was 11.151 microg/mL at 5 min after the intravenous injection and t1/2 was 2.936 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 to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.

Pharmacokinetic study of palonosetron hydrochloride in healthy volunteers / 中国肿瘤临床

Objective: To evaluate the pharmacokinetics of palonosetron hydrochloride in healthy volunteers. Methods: Thir-ty-one healthy volunteers were grouped into three palonosetron hydrochloride dosage regimens of 0.125, 0.25, and 0.5 mg. The plasma concentrations of palonosetron were determined by ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). DAS 2.1 software was applied to assess the plasma concentration-time data. Results:After intravenous injection of 0.125, 0.25, and 0.5 mg palonosetron to the subjects, the AUC0-168h values of palonosetron were (7.5±2.5), (15.2±4.0), and (34.8±9.7) μg· h·mL-1. The t1/2 values were (27.2±9.5), ( 27.2±6.5), and (31.4±5.6) h. Palonosetron exposure increased proportionally with the dose range of 0.125 mg to 0.5 mg. The correlation coefficient was 0.998. No grade 3 or grade 4 toxicity was observed during the study. Con-clusion:A rapid, sensitive, and selective UPLC-MS/MS method for palonosetron quantification in human plasma was developed and validated. All the participants indicated high tolerance throughout the study. Our data showed that palonosetron exhibits linear pharma-cokinetics over the the dose range of 0.125 mg to 0.5 mg.