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Relationship of topical dose and percutaneous absorption in rhesus monkey and man
Abstract:
[14C]Testosterone, [14C]hydrocortisone, and [14C]benzoic acid were applied to skin of the rhesus monkey and man, and percutaneous absorption was quantitated by measuring urinary excretion of 14C. In the rhesus, the concentration of testosterone was increased from 4 to 4000 mug/cm2 in 5 steps. The efficiency of absorption decreased from 18.4 +/- 9.5% to 1.4 +/- 0.8%. However, the total compound absorbed (per cm2 area) always increased, from a low of 0.7mug to 56 mug. In man, testosterone penetration was also dose dependent and very similar to that in rhesus. Increasing the dose of hydrocortisone 10-fold (4 to 40 mug/cm2) resulted in a decrease in efficiency of absorption in man (1.6 +/- 1.4% to 0.6 +/- 0.3%) and rhesus (2.9 +/- 0.8% to 2.1 +/- 0.6%). The total compound absorbed, however, increased manyfold in both species. As benzoic acid concentrations were increased in man from 3 to 2000 mug/cm2, the percent absorption decreased, from 37.0 +/- 16.3% to 14.4 +/- 3.8%. Benzoic acid absorbed increased from 1.1 mug to 288 mug (per cm2 area), representing almost a 300-fold increase in absorption. Values in the rhesus were similar.
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