Intestinal permeability of chlorpyrifos using the single-pass intestinal perfusion method in the rat.
The intestinal transport of chlorpyrifos (CPF), an organothiophosphate pesticide, was investigated using the single-pass intestinal perfusion (SPIP) technique in male, Sprague-Dawley rats. SPIP was performed in each isolated region of the small intestine (i.e. duodenum, jejunum and ileum) with three concentrations of CPF (0.1, 2.0 and 10 microM) at a flow rate of 0.25 ml/min. Preliminary binding and stability studies were conducted to ensure that the loss of CPF in the SPIP study can be attributed to intestinal absorption. The effective permeability (P(eff)) of CPF was determined for each segment and concentration. CPF exhibits a high intestinal permeability over the length of the small intestine indicative of compounds that are well absorbed. Decreases in permeability values at the highest CPF concentration studied in the duodenum and ileum suggest a saturable transport process. Based on these results, passive, transcellular diffusion dominates the intestinal transport mechanism of CPF, with a saturable transport process evident in the duodenum and ileum. The P(eff) of CPF is in the range of drugs with high intestinal permeability and high fraction of dose absorbed indicating that CPF readily crosses the intestine. The dependence of CPF's P(eff) on concentration in the duodenum and ileum suggests that CPF is transported by a combination of mechanisms across the intestine. Using established relationships, the human fraction dose absorbed for CPF was estimated to be >99%. The permeability values obtained from this study may be useful in models of exposure assessment.
Cook
Thomas J
TJ
Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, the State University of New Jersey, Piscataway, NJ 08854, USA. tjcook@rci.rutgers.edu
Shenoy
Smriti S
SS
D000465:Algorithms; D000818:Animals; D004390:Chlorpyrifos / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D007306:Insecticides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007408:Intestinal Absorption / Q000502:physiology*; D008297:Male; D010477:Perfusion; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D013056:Spectrophotometry, Ultraviolet
D007306:Insecticides; D004390:Chlorpyrifos