May 1, 1976

Mirex kinetics in the rhesus monkey. II. Pharmacokinetic model

Drug Metabolism and Disposition : the Biological Fate of Chemicals
K A PittmanD H Treble


14C-Mirex was given iv and po to female rhesus monkeys (Macaca mulatta) and radioactivity was measured in plasma, urine, and feces at intervals after dosing and in tissues when animals were killed. Graphical analysis of plots of the logarithm of plasma concentration vs. time was used to provide estimates of the values of the first-order rate constants required by the proposed pharmacokinetic models. A BASIC-language program, FITKIN, was used to obtain numerical solutions to the differential equations for each model and to adjust the estimates to obtain a normalized, least squares fit. Of several models postulated, a mammillary, four-compartment, open-system model, providing for the urinary excretion of Mirex from a "central" compartment and for the fecal excretion of Mirex from a "fast" tissue compartment, yielded theoretical data in agreement with observed values. This model predicted that the accumulation of Mirex into fat would be retarded by the presence of a "slow" tissue compartment so that distribution equilibrium would take about half a year. From that time to the end of a 5-year projection, little decline in the quantities of Mirex was predicted for any compartment. Sequestration in fat and a lack of metabolism were re...Continue Reading

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Mentioned in this Paper

Metabolic Process, Cellular
Fat Pad
Body Excretions
Metabolic Pathway
Programming Languages
Excretory Function
Anatomical Compartments

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