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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

The effects of terpene enhancers on the percutaneous permeation of drugs with different lipophilicities.

Four model drugs were selected based on their lipophilicity denoted as log P (nicardipine hydrochloride log P -0.99 +/- 0.1, hydrocortisone log P 1.43 +/- 0.47, carbamazepine log P 2.67 +/- 0.38, and tamoxifen log P 7.87 +/- 0.75). The enhancing activities of four terpene enhancers (fenchone log P 2.13 +/- 0.30, thymol log P 3.28 +/- 0.20, D-limonene log P 4.58 +/- 0.23, and nerolidol log P 5.36 +/- 0.38) were tested in vitro across full thickness hairless mouse skin with each of the evaluated drugs formulated in hydroxypropyl cellulose gel formulations. The relationships between lipophilicity (log P) of the terpene enhancers and model drugs and efficacy (represented by the enhancement ratio of flux ER(flux)) of the drugs when coadministered with the enhancers were examined using linear regression. Terpene enhancers had significant effect on the percutaneous permeation of the model drugs. Nerolidol (highest lipophilicity) provided the highest increase in the flux of the evaluated model drugs. The flux of nicardipine hydrochloride increased by approximately 135-fold, hydrocortisone by 33-fold, carbamazepine 8-fold, and tamoxifen 2-fold. The lowest increase in the flux was observed with fenchone. Linear relationships were generated between the ER(flux) of nicardipine hydrochloride, hydrocortisone, carbamazepine, and tamoxifen and the log P of the terpene enhancers [r = 0.951, (P = 0.049), r = 0.977, (P = 0.023), r = 0.942, (P = 0.057), and r = 0.874, (P = 0.126), respectively]. Furthermore, the four terpene enhancers produced linear relationships, indicating that they were more effective at enhancing the penetration of hydrophilic drugs rather than lipophilic drugs r=-0.824 (P=0.176) for fenchone, r = -0.891 (P = 0.109) for thymol, r = -0.846 (P = 0.154) for limonene, and r = -0.769 (P = 0.232) for nerolidol.[1]


  1. The effects of terpene enhancers on the percutaneous permeation of drugs with different lipophilicities. El-Kattan, A.F., Asbill, C.S., Kim, N., Michniak, B.B. International journal of pharmaceutics. (2001) [Pubmed]
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