j. Soc Cosmet. Chem., 48, 277-282 (November/December 1997) Systemic absorption of topically applied carvone: Influence of massage technique N. FUCHS, W. J•GER, A. LENHARDT, L. B(SHM, I. BUCHBAUER, and G. BUCHBAUER, Institute of Pharmaceutical Chemistry, University of Vienna, A/thanstrasse 14, A-1090 Vienna, Austria. Accepted •br publication December 1, 1997. Synopsis In the present study the percutaneous absorption of the cosmetically used fragrance compound (-)-(R)- carvone from a massage oil was investigated. The results showed that (-)-(R)-carvone easily penetrates the skin, exhibiting peak plasma concentrations after about 30 min. Dependent on the massage technique, blood levels and pharmacokinetic parameters significantly changed. While absorption rate constants exhibited no significant differences, the areas under the curve values and the elimination half-lives were significantly higher for the occlusion wrap administration compared to that for the normal massage (+60% and +222%, respectively). The irradiation technique however, failed to increase the penetration of (-)-(R)-carvone through the skin, and so the effect of cosmetic application is therefore doubted. INTRODUCTION The monoterpene (-)-(R)-carvone is found in various plants, but by far the highest concentration is in the oil of spearmint leaves (Mentha spicata var. crispa). Because of its characteristic spicy odor and taste, large amounts are used in cosmetic products (mouth washes, toothpastes) as well as in chewing gums. However, the enantiomer (+)-(S)- carvone, the main constituent in the essential oil of caraway, possesses a typical caraway aroma and is therefore mainly used in the food and fragrance industries. Due to its spasmolytic effect, the essential oil of spearmint leaves is used in many pharmaceutical formulations as a stomachic and carminative agent. In combination with other essential oils, it is applied as a massage treatment and used for baths and inhalations for nervous tension and several skin disorders (1,2). Moreover, this essential oil is also frequently used in aromatherapy massage treatments performed by cosmeticians in cosmetic insti- tutes. In cosmetic treatment, massages have a long tradition and established their indispensable place in the natural therapy concept (3). In spite of its widespread use, no data about the absorption of (-)-(R)-carvone through intact human skin, resulting in measurable blood levels, have been described so far, although data from animal models and from in vitro techniques using cadaver skin exist (4-9), indicating a high rate of absorption for various essential oils. In previous in vivo experiments, we showed that 277

278 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS linalool and linalyl acetate, the main constituents of lavender oil, penetrate human skin, leading to detectable blood levels (10). Therefore, in continuation of our research ac- tivities about the biological fate of fragrance compounds (11), the aim of this study was to investigate the absorption of (-)-(R)-carvone from a massage, using three different massage techniques, and to quantify the concentration of this fragrant in the plasma after ending the cosmetic treatment. MATERIALS AND METHODS CHEMICALS (-)-(R)-carvone (p-Mentha-6,8-dien-2-one optical purity 99%) and racemic piperi- tone (1-methyl-4-isopropyl-l-cylohexen-3-one) were obtained from Roth (Karlsruhe, Germany). Methanol (Lichrosolv ©) was obtained from Merck (Darmstadt, Germany). Peanut oil was purchased from W. Pauli (Vienna) and sodium chloride infusion flask 100 ml (Na + 15.4 mmol, C1- 15.4 mmol and aqua ad injectionem ad 100 ml, pH = 5.0-7.0, 308 mosm/1) from Laevosan (Austria). All other chemicals and solvents were of analytical grade and used without further purification. CH3 CH3 I o , H2C•CH3 3H 3 A i:1 Figure 1. Structures of (-)-carvone and racemic piperitone. The chiral center is marked with an asterisk. MATERIALS Breathing masks (large adult face masks, cat. no. 01065, size 6, lot no. 1362H6 from King Systems Corp., Noblesville, Indiana) were obtained from B + P Beatmungsprodukte GmbH, Neunkirchen, Seelscheid, Germany). Isolute-C18 (EC) columns (100 mg) were purchased from International Sotbent Technology Ltd., Mid Glamorgan, UK. Lithium- heparine vacuum tubes (Vacutainer, 10 ml) were obtained from Becton Dickinson, Meyland Cedex, France, and the irradiation lamp Osram HX 16 (220 V, 60 W) was purchased from Osram fitted with a special filter (golden amber, transmission of 43% between the wavelengths of 620 and 660 nm Osram, Vienna, Austria). EXPERIMENTAL CONDITIONS One and one-half gram of massage oil containing 20% (w:w) (-)-(R)-carvone in peanut