Gastrointestinal transit mathematical model in mice treated with antibiotics

Fecal 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 & NOTEWORTHY This 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. ### Competing Interest Statement The authors have declared no competing interest. * M a : Antibiotic mass in the stomach M b : Antibiotic mass in the cecum C b : Antibiotic concentration in the cecum. C : Antibiotic concentration in feces q : Orally administered antibiotic mass α : Rate of elimination from the stomach k a : Elimination rate constant from the stomach k b : Elimination rate constant from the cecum A : Mass of the contents of the cecum t b : Time it takes for all the antibiotic in the stomach to be eliminated Δ t 1 : Time for the antibiotics to appear in the cecum the time for the antibiotics to appear in the cecum Δ t 2 : Time between leaving the cecum and being eliminated as feces t S : Intestinal transit time (=The time for the oral dose to be eliminated as feces)