Physiologically based pharmacokinetic modeling using various pharmacokinetic models to predict the pharmacokinetics of the anti-tumor agent, dacarbazine, in rats

Pharmacokinetic characteristics of dacarbazine was examined using rats and the behavior of dacarbazine in the body was stimulated using a pharmacokinetic model analysis method to provide basic pharmacokinetic information. The pharmacokinetics of dacarbazine follows a two-compartment pharmacokinetic model and was highly distributed to the liver and kidney. Based on these results, the physiologically based pharmacokinetic model was constructed. The dacarbazine concentration-time profiles in the heart and brain were almost the same as those in the plasma, whereas the time courses in the liver and kidneys decreased more slowly. The concentrations in the plasma and examined tissues decreased to 0.3–0.6% of the maximum concentrations 360 min after administration. Therefore, no accumulation of dacarbazine was observed in the body at once daily administration.