ABSORPTION OF CARVONE 281 40- 30- 10- O: -a- normal masage • ß occlusion wrap ' _ , o Time (min) Figure 2. Plasma levels of (-)-carvone in human blood in dependence on three different massage tech- niques. Table I Pharmacokinetic Parameters for (-)-Carvone Parameter Normal massage Occlusion wrap Irradiation C•,a• (ng) 23.92 + 2.32 32.56 + 3.35 28.31 + 4.01 tma x (min) 25.81 + 3.05 36.65 + 4.87* 23.49 + 4.35 ka (l/h) 2.34 + 0.53 2.23 + 0.29 1.82 + 0.22 t•/2,• (min) 7.80 + 2.27 9.21 _+ 1.96 6.69 + 2.87 t•/2• (min) 33.49 + 6.10 74.45 + 15.62' 26.81 + 4.93 AUC (ng/ml x min) 1713 + 28 2746 + 33* 1843 + 113 Each value represents the mean _+ SD of three massages. * Significantly different from normal massage and irradiation technique (p 0.05). range from 1.82 to 2.34 h -1, indicating the same half lives of absorption, the values for the time to reach the peak concentration tma x (23.49--36.65 min, respectively) and the blood levels from 30 to 100 min for the occlusion wrap administration, were signifi- cantly higher than those for normal massage and the irradiation technique. The distri- bution half-life tl/2• was short (7.80-9.21 min). The elimination half life tl/2[ 3 was significantly longer (2.2-2.7 times) when an occlusion wrap was used. In conclusion, (-)-(R)-carvone rapidly penetrates the skin of a human subject, resulting in measurable blood levels. Therefore, topical application of (-)-(R)-carvone should be carried out only under consideration of the high absorption rate. The irradiation method failed to increase topical absorption of (-)-(R)-carvone, and so the effect of cosmetic

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