title: Clinical pharmacology research strategy for dissolvable tobacco products.
abstract: BACKGROUND
  Dissolvable tobacco products (DTPs) are relatively new to the market. Some researchers and manufacturers describe them as finely ground tobacco that has been compressed into sticks, strips, and orbs that dissolve or disintegrate in the mouth and do not require spitting. While the pharmacokinetic profiles of nicotine and other tobacco-associated compounds and pharmacological effects of these products are complex, their clinical pharmacology has not been systematically evaluated. We reviewed the scientific literature regarding the known pharmacokinetic (PK) characteristics and pharmacodynamic (PD) effects of DTPs with the purpose of identifying research gaps and informing future studies.
  
  
  OBJECTIVE
  To evaluate current knowledge of the pharmacological properties of DTPs; to assess their similarities and differences with other tobacco products, especially smokeless tobacco products, and Food and Drug Administration-approved nicotine replacement therapies; to identify gaps in existing information; and to propose a strategy for future clinical pharmacology studies of DTPs.
  
  
  METHODS
  We reviewed the peer-reviewed literature and generated research questions for future clinical pharmacology studies.
  
  
  CONCLUSIONS
  Data on the PK and PD of DTPs are sparse and inconsistent. The results of existing studies are limited and inconclusive, and their interpretation is complicated by methodological and/or study design issues. This review identifies a need for larger, comprehensive, and prospectively designed studies that include PK/PD measurements and data analyses. We propose a research agenda for future DTP studies related to the clinical pharmacology of nicotine, its metabolites, tobacco-specific nitrosamines, and other toxic compounds.
authors.affiliation: Office of Science, Center for Tobacco Products, Food and Drug Administration, Rockville, MD.
authors.forename: Elena V
authors.initials: EV
authors.lastname: Mishina
authors.forename: Allison C
authors.initials: AC
authors.lastname: Hoffman
mesh_terms: D002986:Clinical Trials as Topic; D006801:Humans; D010599:Pharmacokinetics; D014030:Tobacco, Smokeless / Q000032:analysis; D014481:United States