Development of a Pharmacokinetic Description of Lipophilic Chemical Transport inMammary Tissues

摘要

This study developed a pharmacokinetic description to describe the excretion oflipophilic contaminants into breast milk. Areas of interest included the pathways in, which contaminants are transferred in breast milk and the development of physiologically based pharmacokinetic model equations to describe these pathways. A literature search revealed that while a few studies had addressed the passage of pharmaceutical drugs into breast milk, the exact excretion mechanisms were not well understood. In general the literature assumed that transfer of drugs occurred by passive diffusion. This assumption was applied to xenobiotics without regard to the difference between pharmaceutical drugs and environmental contaminants, especially lipophilic contaminants. This work developed equations to describe (1) the passive diffusion of unbound lipophilic contaminants into milk; (2) the passive diffusion of lipophilic contaminants bound to fat, and (3) the carrier mediated transport of lipophilic contaminants bound to fat. Transport was described by expressions for the mass balance of HCB entering and leaving the mammary tissue. For carrier mediated transport, the amount entering the tissue was described by a Michaelis-Menten type expression for saturable kinetics. The results of this work illustrated that the possible mechanisms of contaminant transport into mammary tissue can be described by simple mass balance equations Mammary pharmacokinetics, Lipophilic chemical transport, Physiologically based pharmacokinetics, Pbpk.