Effect of Lipophilicity on in Vivo Iontophoretic Delivery. I. NSAIDs
| Autor: | Yasuki Kato, Kunio Itoh, Eiji Hayakawa, Yoshikazu Tashiro, Shozo Shichibe |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Ketoprofen Naproxen Chemical Phenomena Pharmaceutical Science Absorption (skin) Pharmacology Administration Cutaneous Rats Sprague-Dawley Pharmacokinetics In vivo medicine Animals Chromatography High Pressure Liquid Skin integumentary system Iontophoresis Chemistry Physical Chemistry Anti-Inflammatory Agents Non-Steroidal General Medicine Lipids Rats Lipophilicity Drug metabolism medicine.drug |
| Zdroj: | Biological and Pharmaceutical Bulletin. 24:278-283 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | The effect of drug lipophilicity on in vivo iontophoretic transdermal absorption was evaluated. Non-steroidal anti-inflammatory drugs (NSAIDs) were selected as model drugs with a wide range of lipophilicity: salicylic acid (SA), ketoprofen (KP), naproxen (NP) and indomethacin (IM). Cathodal iontophoresis of NSAIDs was conducted in rats (0.625 mA/cm2; 90 min), and drug concentrations in skin, cutaneous vein and systemic vein were determined. Skin concentrations of NSAID were higher in the case of lipophilic drugs (SA=KP=NPIM), whereas cutaneous plasma concentrations decreased with an increase in lipophilicity (SAKP=NPIM). Additionally, the dependence of drug lipophilicity on systemic plasma concentration was similar to cutaneous plasma concentration. The transfer rate from skin to cutaneous vein (R(SC)) was calculated from the arterio-venous plasma concentration difference of drug in the skin. Normalized R(SC) by skin concentration (R(SC)/X(S)) yielded a negative correlation with the logarithm of n-octanol/buffer partition coefficient (Log P at pH 7.4), suggesting that transfer of NSAIDs from skin to cutaneous vein decreased with increasing lipophilicity (SAKP=NPIM). This correlation means that drug partitioning between stratum corneum and viable epidermis might be a dominant step. |
| Databáze: | OpenAIRE |
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