Effect of Menthol on Nicotine Pharmacokinetics in Rats After Cigarette Smoke Inhalation

The effect of menthol on nicotine disposition is important in understanding smoking behaviors among different racial groups. The present study was to evaluate whether menthol affects the pharmacokinetics of nicotine after cigarette smoke inhalation. Rats were exposed to mainstream smoke from either a nonmentholated or mentholated cigarette (1 puff/min for 10 min) using a smoke inhalation apparatus. For the multiple-cigarette smoke inhalation, rats received the smoke from either nonmentholated or mentholated cigarette (10 puffs) every 12 hr for a total of 17 cigarettes. Serial blood samples were collected during the 10-min inhalation phase for the single-cigarette smoke or the 17th cigarette inhalation and for 30 hr thereafter. Nicotine and its major metabolite cotinine were assayed by radioimmunoassay methods. Following single-cigarette smoke inhalation, mentholated cigarettes significantly decreased the mean peak concentrations of nicotine in plasma (C-max) from 27.1 to 9.61 ng/ml and the total area under the plasma concentration-time curves (AUC) from 977 to 391 ng min/ml as compared with those after nonmentholated cigarette smoke inhalation. C-max and AUC values for cotinine were also significantly reduced by menthol. Similarly after multiple smoke inhalation, C-max, AUC, and the mean average steady-state plasma concentration of nicotine as well as cotinine were significantly lower in mentholated cigarette inhalation. Interestingly, there was a significant increase in the cotinine to nicotine AUC ratio from 13.8 for the nonmentholated to 21.1 for the mentholated cigarette. These results suggest that menthol in mentholated cigarettes can substantially decrease the absorption and/or increase the clearance of nicotine.