A compartment model for the membrane-coated fiber technique used for determining the absorption parameters of chemicals into lipophilic membranes.
Xia-XR; Baynes-RE; Monteiro-Riviere-NA; Riviere-JE
Pharm Res 2004 Aug; 21(8):1345-1352
Purpose. The purpose of this work was to develop a compartment model for the membrane-coated fiber (MCF) technique for determining the absorption parameters of chemicals into lipophilic membranes. Methods. A polymer membrane coated onto a section of inert fiber was used as a permeation membrane in the MCF technique. When MCFs were immersed into a donor solution, the compounds in the solution partitioned into the membrane. At a given permeation time, a fiber was removed from the solution and transferred into a gas chromatography injector for quantitative analysis. The permeation process of a given chemical from the donor phase into the membrane was described by a one-compartment model by assuming first-order kinetics. Results. A mathematical model was obtained that describes the cumulative amount of a chemical permeated into the membrane as a function of the permeation time in an exponential equation. Two constants were introduced into the compartment model that were clearly defined by the physiochemical parameters of the system (a kinetic parameter and the equilibrium absorption amount) and were obtained by regression of the experimental data sampled over a limited time before equilibrium. The model adequately described the permeation kinetics of the MCF technique. All theoretical predictions were supported by the experimental results. The experimental data correlated well with the mathematical regression results. The partition coefficients, initial permeation rate, uptake, and elimination rate constants were calculated from the two constants. Conclusions. The compartment model can describe the absorption kinetics of the MCF technique. The regression method based on the model is a useful tool for the determination of the partition coefficients of lipophilic compounds when it takes too long for them to reach permeation equilibrium. The kinetic parameter and the initial permeation rate are unique parameters of the MCF technique that could be used in the development of quantitative structure-activity relationship models.
Skin-absorption; Diffusion-analysis; Fiber-deposition; Gas-chromatography; Mass-spectrometry; Mathematical-models; Computer-models; Computer-software; Analytical-models; Analytical-chemistry
Xin-Rui Xia, Center for Chemical Toxicology Research and Pharmacokinetics (CCTRP), College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, 27606
Disease and Injury: Allergic and Irritant Dermatitis; Work Environment and Workforce: Mixed Exposures
North Carolina State University, Raleigh, North Carolina