Computer simulation of mirex pharmacokinetics in the rat

Abstract

The iv and po pharmacokinetics of mirex in the rat were examined. Albino female rats were dosed po or iv with approximately 10 mg/kg [14C]mirex (1.45 mCi/mmole). Serial blood, urine, and fecal samples were taken from each animal for 3 weeks. Cumulative urinary elimination 3 weeks after treatment was less than 1% of the administered dose for either route of exposure. Cumulative fecal elimination 3 weeks after treatment was less than 7% following iv exposure but was 18 to 45% for po-dosed animals. However, in po-dosed rats most of the fecal mirex was recovered within 48 hr of treatment and was therefore attributed to elimination of nonabsorbed mirex. A three-compartment, open system model with parallel first-order elimination into the urine and feces was developed to simulate mirex pharmacokinetics after either iv or po administration. All data were simulated on an analog-digital hybrid computer by simultaneous integration of the differential equations describing the model. The computer simulation established lines of best fit for blood, urine, and feces experimental data while projecting mirex levels in the two peripheral compartments. Computer simulation of iv mirex pharmacokinetics predicted that mirex was quickly cleared from the blood into the rapidly equilibrating compartment. Over the next several weeks, mirex was redistributed to a slowly equilibrating compartment which acted as a depot for mirex storage. Computer simulation of the po-dosed animals required the introduction of a time lag in mirex absorption. Following absorption, the projected mirex distribution pattern resembled that of the iv-dosed animals with the slowly equilibrating compartment retaining most of the mirex. © 1982.