No Effect of Albumin on the Dermal Absorption Rate of Hydrocortisone 21-Butyrate, Permethrin or Diflunisal in the Isolated, Single-Pass Perfused Rabbit Ear

Abstract

Rabbit ears were single-pass perfused with a buffer solution containing either 6% hetastarch or 5% bovine serum albumin. Hydrocortisone 21-butyrate (5 mM), diflunisal (17 mM) or permethrin (33 mM) was added to isopropyl myristate with 5% polyethylene, and applied to about 40% of the epithelial surface area of the ear. Hydrocortisone 21-butyrate or permethrin were not found in the effluent with hetastarch or albumin. Following cutaneous ester hydrolysis, the appearance rate of hydrocortisone was about 4 pmol/min per cm² in the hetastarch- or the albumin-containing buffer solution. No hydrolysis of permethrin was detected; the appearance rate of 3-phenoxybenzyl alcohol with 3-phenoxybenzoic acid corresponded to the absorption rate of the substrate impurities. During ex vivo perfusion of intact skin, serum albumin in the perfusion fluid may not enhance the appearance rate of xenobiotics in the effluent following dermal application when the distribution coefficient n-octanol/water is > 2,000 or when the xenobiotic is ionized at physiological pH. In general, for all substances investigated with our perfusion model thus far, the appearance rates decreased with rising distribution coefficient (n-octanol/buffer pH 7.4). High lipophilicity hinders the release from isopropyl myristate and the penetration through the skin.

Effects of experimental conditions on absorption of glycol ethers through human skin in vitro

“…The effects of receptor fluid on penetration are well researched for lipophilic compounds. DeLange et al (1994) showed that penetration of xylene in a perfused pig ear organ model was dependent on the protein content of the receptor fluid, though the influence of the receptor fluid depended on the penetrating compound (Bast and Kampffmeyer 1996;Pelling et al 1998). It is unexpected, however, to find such an effect for relatively hydrophilic compounds such as EE and BE.…”

Absorption and Metabolism of (all-trans-) Retinol Acetate, Retinol, and Retinoic Acid in the Single-Pass, Albumin-Perfused Rabbit Ear

“…In previous experiments with 5% BSA in the perfusion fluid [1] the absorption of hydrocortisone 21-butyrate, permethrin, or diflunisal was not enhanced compared with 6% hetastarch. In the present experiments with retinoids, however, we only detected percutaneous absorption in the presence of BSA.…”

“…The highest application density of these impurities, concomitant with the substrate, and their percutaneous absorption rates have led the calculated appearance rates of these impurities to be 6 five times below the detection limit. The origin of all the other substances has been described elsewhere [1,5].…”

“…Previously, we have described absorption and metabolic rates of several xenobiotics in relation to their distribution coefficients (noctanol/buffer, pH 7.4) in the single-pass perfused rabbit ear [1]. Substrates lacking a hydrophilic group at physiological pH 7.4, and a distribution coefficient 1110 3 (hydrocortisone 21-butyrate and permethrin) showed no percutanous absorption.…”

Influence of solubility and permeant size on absorption and metabolism of xenobiotics in rabbit skin

“…Procaine and hydrocortisone 21-hemisuccinate are ionized at physiological pH and so are more soluble in the perfusion buffer. This might also apply to diflunisal and 3-phenoxybenzoic acid which reached high steady-state absorption rates (1600 pmol/min per cml 11 and 600 pmol/min per cm2 12 respectively, normalized for 10 mM substrate concentration in isopropyl myristate) although we did not look for their metabolites.…”