Biol. Pharm. Bull. 28(5) 870—875 (2005)

cally as it 1) has a rapid onset and cessation of effect upon intravenous infusion, 2) accumulates little and induces a brief but profound anesthesia, 3) maintains a level in the circulation similar to the levels achieved by inhalation anesthetics. Since PF is formulated as an intravenous emulsion containing soybean oil and egg yolk lecithin, it causes problems of pain at the site of injection and a considerable fat load. As an alternative route of administration to prevent the side effects of injection, a transdermal therapeutic system seems to be attractive. However, the stratum corneum is known to be a major barrier to drug permeation through the keratinized epithelium. Owing to the poor skin penetration of drugs, topical administration is often limited and not very effective. Furthermore, when using PF as an anesthetic, strict control of the drug concentration in blood is needed. However, as the blood level of the drug can be maintained for an extended period of time after transdermal administration of PF, continuous sedation may be obtained. Hence, it is possible that PF can be developed as a sedative or a hypnotic administered transdermally. For the development of a transdermal therapeutic form, a drug appropriate for transdermal delivery should be chosen. The most readily permeating drugs are small molecules of moderate lipophilicity. It is known that a parabolic dependence is often found between skin permeation and octanol–water partition coefficient (P). Yano et al. reported that the optimum log P value of nonsteroidal antiinflammatory drugs for transdermal absorption was 2—3. The log P value of PF listed in the drug information form prepared by Astra Zeneca is 3.8, and PF is a low molecular compound (MW 178.27). Furthermore, as PF exists in the liquid state above 20 °C, high-concentration PF solutions can be prepared. Hence, it is considered that PF is a promising drug for transdermal delivery. In this study, we examined the skin permeability in rats of PF in a liquid state and in solutions containing isopropyl myristate (IPM), ethanol or propylene glycol (PG). Furthermore, to evaluate the pharmacological effects of the topical application of PF, we prepared PF ointments as a simple dosage form that could be applied to unanesthetized rats, and evaluated the relationship between plasma PF concentration and sedative effect.