Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
Regular Article
Evaluation of Percutaneous Absorption of Midazolam by Terpenes
Yusuke OTAAkinobu HAMADAMasahiro NAKANOHideyuki SAITO
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2003 Volume 18 Issue 4 Pages 261-266


Midazolam is a highly lipophilic drug that is widely used in preanesthetic medication. Recently, terpenes have been reported to show an enhancing effect on percutaneous absorption of drugs. The effect of terpenes (l-menthol, d-limonene, RS-(±)-β-citronellol, geraniol) on the in vitro percutaneous absorption of midazolam through rat skin was evaluated using unjacketed Franz diffusion cells. Since midazolam is a lipophilic drug, percutaneous penetration is low and a percutaneous penetration enhancer is necessary for its percutaneous absorption. The terpenes (5%, w/v) in combination with 30% ethanol, and 20% propylene glycol significantly increased the percutaneous absorption of midazolam in comparison to the control. In vitro data suggested that d-limonene is the most effective enhancer among terpenes and other penetration enhancers such as Azone®. In in vivo percutaneous absorption assays, the midazolam formulation using d-limonene could penetrate through rat skin, but the other terpenes could not penetrate. In conclusion, d-limonene in combination with ethanol can be used to enhance the percutaneous absorption of the highly lipophilic drug midazolam.

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© 2003 by The Japanese Society for the Study of Xenobiotics
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