Percutaneous Absorption of Vanilloids: In Vivo and in Vitro Studies

• Published in: Journal of pharmaceutical sciences Vol. 86; no. 1; pp. 142 - 146
• Main Authors: Kasting, Gerald B., Francis, William R., Bowman, Lisa A., Kinnett, Gene O.
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.01.1997; John Wiley & Sons, Inc; Wiley; American Pharmaceutical Association
• Subjects: Animals; Biological and medical sciences; Capsaicin - analogs & derivatives; Capsaicin - pharmacokinetics; General pharmacology; Humans; In Vitro Techniques; Male; Medical sciences; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Rats; Skin Absorption; Vanillic Acid - analogs & derivatives; Vanillic Acid - pharmacokinetics; Human; Rat; Capsaicin; Rodentia; Elimination; Permeability; Metabolism; Nonane derivatives; In vitro; Olvanil; Percutaneous route; Lipophilic compound; In vivo; Vertebrata; Mammalia; Absorption; Animal; Skin; Pharmacokinetics
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1021/js950484a

The percutaneous absorption of three highly lipophilic analogs of capsaicinsvanillylnonanamide (VN), olvanil, and NE-21610swas measured in vivo in the CD:VAF rat, and in vitro through excised CD: VAF and SkH:Fz rat skin and human cadaver skin. Absorption and skin metabolism were monitored by radiolabel techniques. The rank order of penetration in all species was VN>olvanil>NE-21610, in accordance with that expected from their physical properties. Rat skin was more permeable than human skin by factors ranging from 4 to 8 for VN, 10 to 20 for olvanil, and ≈10 to 100 for NE-21610. All three compounds were extensively metabolized during passage through fresh SkH:Fz rat skin, with the primary route of degradation for at least two of the compounds involving hydrolysis of the amide bond (the metabolites of NE-21610 were not identified). For the in vitro studies a range of receptor solutions was employed to determine a set of conditions that best mimicked in vivo absorption. The results with phosphate-buffered saline containing a preservative and 1–6% polyoxyethylene-20 oleyl ether (Oleth-20) were in good agreement with in vivo results for all three compounds for periods up to 24h post-dose; after this time, in vivo absorption rates declined but in vitro rates remained relatively constant. Buffered saline or saline containing 0.5% bovine serum albumin led to marked underestimates of in vivo penetration for olvanil and NE-21610, whereas a 1:1 ethanol: water solution led to gross overestimates of the in vivo absorption rates for all three compounds.