Modelling Dermal Pharmacokinetics Using in vitro Data Part I. Fluazifop-butyl in the Rat

Abstract

The pharmacokinetics of the herbicide fluazifop-butyl have been determined in female rats following oral and intravenous dosing, and described by a mathematical model. Penetration of fluazifop-butyl through epidermal membranes has been determined using three different receptor fluids. It is demonstrated how this in vitro absorption data can be used with a pharmacokinetic model derived from oral and i.v. dosing studies to predict plasma concentrations and urinary excretion profiles following dermal dosing. Model predictions are compared with experimental measurements and found to be in good agreement.

Get full access to this article

View all access options for this article.

References

Auton TR , Ramsey JD & Woollen BH Modelling dermal pharmacokinetics using in vitro data. Part II. Fluazifop-butyl in man. Human and Experimental Toxicology (This volume)

Scott RC & Ramsey JD

Comparison of in vivo and in vitro percutaneous absorption of a lipophilic molecule (Cypermethrin, a pyrethroid insecticide). Journal of Investigative

Dermatology 1987; 89: 142-6.

Dugard PH , Walker M. , Maudsley SJ & Scott RC Absorption of some glycol ethers through human skin in vitro. Environmental Health Perspectives 1984; 57: 193-7.

Bronaugh RL & Stewart RF Methods for in vitro percutaneous absorption III. Hydrophilic compounds . Journal of Pharmaceutical Science 1984; 73: 1255-8.

Grissom RE , Brownie C. & Guthrie FE In vivo and in vitro dermal penetration of lipophilic and hydrophilic pesticides in mice. Bulletin Environmental Contamination Toxicology 1987; 38: 917-24.

Dyer A. , Hayes GG , Wilson JG & Catterill R. Diffusion through skin and model systems. International Journal of Cosmetics Science 1979; 1: 91-100.

Advanced Continuous Simulation Language- Reference Manual Ed. 4.2. Mitchell and Gauthier Assoc ., Concord, Mass., 1987.

Scott RC Percutaneous absorption in vivo:in vitro comparisons. Pharmacology and the Skin, vol. 1. Ed. B. Shroot and H. Schaefer. S Karger, Basel , 1987, pp. 103-110.

Bronaugh RL , Collier SW , Storm JE , Nathan DL & Stewart RF In vitro absorption/metabolism studies in human and animal skin. In: Prediction of Percutaneous Penetration: Methods, Measurements, Modelling. Eds Scott RC , Guy RH & Hadgraft J. IBC, London, 1990, pp. 58-73.