Camphor, menthol, and methyl salicylate occur in numerous over-the-counter products. Although extensively used, there have been no estimates of human exposure following administration via dermal application. Furthermore, there is little information about the pharmacokinetics of those compounds. The authors report the plasma concentrations of the intact compounds as a function of dose following dermal patch application. Three groups of 8 subjects (4 male, 4 female) applied a different number of commercial patches (2, 4, or 8) to the skin for 8 hours. Plasma samples were assayed using sensitive and selective gas-chromatographic methods. For the 8-patch group, the average maximum plasma concentrations (Cmax +/- SD) were 41.0 +/- 5.8 ng/mL, 31.9 +/- 8.8 ng/mL, and 29.5 +/- 10.5 ng/mL for camphor, menthol, and methyl salicylate, respectively. The corresponding values for the 4-patch group were 26.8 +/- 7.2 ng/mL, 19.0 +/- 5.4 ng/mL, and 16.8 +/- 6.8 ng/mL. The harmonic mean terminal half-lives were 5.6 +/- 1.3 hours, 4.7 +/- 1.6 hours, and 3.0 +/- 1.2 hours for camphor, menthol, and methyl salicylate, respectively. The 2-patch group had measurable but low plasma concentrations of each compound. Low-dose dermal application for an extended time results in low plasma concentrations of all 3 compounds. Four and 8 patches, when applied for 8 hours, gave measurable and nearly proportional plasma concentrations. Although unable to determine the absolute dermal bioavailability of these compounds, there appears to be relatively low systemic exposure to these potentially toxic compounds, even when an unrealistically large number of patches are applied for an unusually long time.

No abstract

No abstract

As part of a study to examine cocaine disposition and interaction with ethanol, it was necessary to characterize various properties of cocaine in the blood of the experimental animal. All studies were conducted using blood from healthy adult male Sprague-Dawley rats. Cocaine was incubated in whole blood at 37 degrees C at concentrations of 500-4000 ng/mL. The apparent first-order rate constant for cocaine loss was independent of concentration. Blood clearance, calculated assuming blood volume to be 64 mL/kg, was estimated to be 0.056 +/- 0.003 mL/(min.kg); a value considerably smaller than estimates of systemic clearance. The addition of NaF increased the rate of loss to form benzoylecgonine, as a result of increased chemical degradation and as a consequence of increased pH (to pH 8.0 over 30 h). This NaF-enhanced degradation was abolished when NaF was added to blood buffered to pH 7.4. Ethanol had no influence on cocaine degradation, and there was no evidence of cocaethylene (ethylcocaine) formation. Blood to plasma ratios determined in spiked and authentic samples were constant (0.94-1.05 and 0.99-1.03, respectively) and independent of concentration (100-1500 ng/mL) and pH (7.2-7.6). This ratio was not influenced by NaF or ethanol. The unbound fraction (fu) of cocaine determined in spiked plasma varied from 0.62 to 0.63 over the concentration range (75-2025 ng/mL). Ethanol had no effect on binding. The values for fu determined from authentic blood samples taken from rats dosed intravenously with cocaine (10 mg/kg) ranged from 0.67 to 0.69 (over the concentration range 300-1500 ng/mL). Cocaine plasma protein binding was independent of concentration but depended upon plasma pH (fu, 0.765 and 0.486, at pHs 7.0 and 7.8, respectively.

No abstract