Review of the evidence that pH is a determinant of nicotine dosage from oral use of smokeless tobacco

Objective - To determine whether manipulation of the pH of moist-snuff products by manufacturers could control the delivery of nicotine. Data sources - Medline database 1966-97 using the following subject headings and keywords: nicotine, absorption, mouth mucosa, skin, hydrogen-ion concentration, smokeless tobacco, biological transport, and membranes; computer database of the tobacco bibliography maintained by the US Centers for Disease Control and Prevention's Office on Smoking and Health; bibliographies of pertinent journal articles, books, and governmental reports; personal communications with experts in nicotine pharmacology and addiction; and Brown & Williamson Tobacco Corporation documents in the Tobacco Control Archives of the University of California, San Francisco. Study selection - Included all relevant animal studies, in-vitro studies, nicotine replacement therapy trials, and human observational studies. Data synthesis - We found that the effects of pH on drug absorption have been well established in animal models for nicotine and many other acidic or basic compounds. Increased alkalinity promotes the absorption of nicotine and increases its physiological effects. Human studies, which are more limited, confirm these processes. For example, nicotine absorption is directly related to the pH when nicotine is delivered in either tobacco smoke or nicotine polacrilex gum. Conclusions - Although other factors could influence the rate of nicotine absorption from oral tobacco, manipulating tobacco pH appears to be the primary means by which the speed of nicotine absorption is determined in moist-snuff products.