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A quantitative study was undertaken to assess the plasma and tissue levels, tissue distribution and skin (ear) absorption of the sesquiterpene alpha-humulene, the main active constituent isolated from the plant Cordia verbenacea (Boraginaceae ), after oral, intravenous and topical administration in mice. The alpha-humulene levels were quantified by GC-MS analysis. The peak alpha-humulene concentration was achieved 15 min following its oral administration (150 mg/kg). Then, the alpha-humulene plasma concentration gradually decreased and it was almost undetectable at 2 hours after intravenous administration and 12 hours after oral administration. When the oil of C. verbenacea was given orally (1 g/kg), the peak alpha-humulene plasma concentration was observed after 30 min, being detectable only up to 2 h. The oral bioavailability of alpha-humulene was found to be 18 %. The half-lives of alpha-humulene were very short, 16.8 min after oral administration and 1.8 min after intravenous administration. However, the elimination half-lives were longer, 118.2 min and 55 min, for oral and intravenous routes, respectively. We also assessed the amount of alpha-humulene in some selected tissues at 0.5 and at 4 h after oral administration. We found a high amount of the compound in the liver, followed by the kidneys, heart, lungs, spleen and brain, 0.5 h after oral administration. Notably, the yield of alpha-humulene decreased significantly in all analyzed tissues, especially in the liver, 4 h after oral administration. Of note, 30 minutes after topical administration of Acheflan formulations (cream and aerosol) containing 0.5 % of C. verbenacea essential oil, a schedule of treatment that produces marked and similar topical anti-inflammatory activity, the amount of alpha-humulene absorbed in the ear was very similar (about 2 microg/ear). It is concluded that alpha-humulene exhibited a rapid onset and relatively good absorption following oral and topical administration. Taken together, these findings further contribute to an explanation of the topical and systemic anti-inflammatory and antinociceptive properties previously reported for the essential oil and for alpha-humulene obtained from Cordia verbenacea, they also provide support for the clinical studies conducted with the phytomedicine Acheflan.