P A Kothare1, C L Zimmerman. 1. Department of Pharmaceutics, University of Minnesota, Minneapolis 55455, USA.
Abstract
PURPOSE: To evaluate the aqueous transfer model as the mechanism for the micelle-mediated uptake of phenol in the rat in situ intestinal perfusion model. METHODS: Phenol in isotonic HEPES buffer was perfused through the jejunal segment at two flow rates and at various concentrations. Phenol was then dispersed in two, distinct mixed micelle systems composed of sodium taurocholate and phosphatidylcholine at 10 mM:2.5 mM (10:2.5 system) and at 10 mM: 10 mM (10:10 system) and its uptake studied in each case. Equilibrium dialysis was done to determine the aqueous fraction of phenol in each system. RESULTS: The P(eff) of phenol in isotonic HEPES buffer at a low flow rate (n = 6) was 1.7 +/- 0.4 x 10(-4) cm/s and at a high flow rate (n = 13) was 1.8 +/- 0.5 x 10(-4) cm/s. The P(eff) for the 10:2.5 system at the high flow rate (n = 3) was 1.5 +/- 0.4 x 10(-4) cm/s and at the low flow rate (n = 3) was 1.4 +/- 0.3 x 10(-4) cm/s. Uptake was membrane rate-limited in both the non-micellar and 10:2.5 systems. P(eff) at a high flow rate (n = 3) in the 10:10 system was 1.3 +/- 0.1 x 10(-4) cm/s. Equilibrium dialysis (n = 4) revealed free fractions of 0.60 +/- 0.05 and 0.50 +/- 0.03 for the 10:2.5 and 10:10 systems. CONCLUSIONS: The uptake of micellized phenol did not follow the aqueous transfer model of uptake.
PURPOSE: To evaluate the aqueous transfer model as the mechanism for the micelle-mediated uptake of phenol in the rat in situ intestinal perfusion model. METHODS:Phenol in isotonic HEPES buffer was perfused through the jejunal segment at two flow rates and at various concentrations. Phenol was then dispersed in two, distinct mixed micelle systems composed of sodium taurocholate and phosphatidylcholine at 10 mM:2.5 mM (10:2.5 system) and at 10 mM: 10 mM (10:10 system) and its uptake studied in each case. Equilibrium dialysis was done to determine the aqueous fraction of phenol in each system. RESULTS: The P(eff) of phenol in isotonic HEPES buffer at a low flow rate (n = 6) was 1.7 +/- 0.4 x 10(-4) cm/s and at a high flow rate (n = 13) was 1.8 +/- 0.5 x 10(-4) cm/s. The P(eff) for the 10:2.5 system at the high flow rate (n = 3) was 1.5 +/- 0.4 x 10(-4) cm/s and at the low flow rate (n = 3) was 1.4 +/- 0.3 x 10(-4) cm/s. Uptake was membrane rate-limited in both the non-micellar and 10:2.5 systems. P(eff) at a high flow rate (n = 3) in the 10:10 system was 1.3 +/- 0.1 x 10(-4) cm/s. Equilibrium dialysis (n = 4) revealed free fractions of 0.60 +/- 0.05 and 0.50 +/- 0.03 for the 10:2.5 and 10:10 systems. CONCLUSIONS: The uptake of micellized phenol did not follow the aqueous transfer model of uptake.