Gastrointestinal transit mathematical model in mice treated with antibiotics

Abstract

ABSTRACTFecal pharmacokinetics is crucial in developing treatment design and evaluating gastrointestinal motility; however, it has not been yet elucidated. This study aimed to elucidate the fecal pharmacokinetics in mice orally administered vancomycin and establish a pharmacokinetic model with interpretable system parameters. In this study, we quantified the antibiotic concentrations in fecal samples collected at high frequency from C57BL/6J mice treated with single oral doses of low and high (1 and 20 mg/mL) concentrations of vancomycin. Samples were taken at approximately 4-hour intervals after administration of antibiotics, making it possible to track the dynamics of vancomycin in the feces with high resolution. Mice structurally pool contents in the stomach and cecum, so we constructed an intestinal transit model that compartmentalizes these organs. Two models were built based on the functional form of gastric content elimination, and physiological parameters such as gastric emptying and intestinal transit time were estimated using high-resolution actual data from each mouse. Fortunately, both models were suitable for evaluating the antibiotic concentrations in feces. By simulation, we confirmed that our estimates of model parameters, which are quite difficult to measure experimentally, are satisfactory. Importantly, this study is applicable to fundamental research relating to pharmacokinetics in the gastrointestinal tract.NEW & NOTEWORTHYThis study tracked the pharmacokinetics of orally administered vancomycin by measuring its concentration in feces and described it using a mathematical model based on the physiological characteristics of mice to replicate these dynamics. As a predictive model, it allows for estimation of drug dynamics outside of the sampling time and extrapolation to individuals with different physiological characteristics.