title: Oral adherence monitoring using a breath test to supplement highly active antiretroviral therapy.
abstract: A breath-based adherence system to document ingestion of oral medications (e.g., HAART) was investigated. Specifically, the food additive 2-butanol, which can be easily packaged with a drug, is converted via alcohol dehydrogenase to the volatile metabolite 2-butanone that rapidly appears in breath, indicating adherence. In healthy adults using a portable sensor and GC-MS, the following experiments were performed: yield of 2-butanone in breath following ingestion of 2-butanol, adherence system accuracy, and potential interference of the adherence system by food or misplacement of 2-butanol on the tongue. During feasibility testing, every subject exhaled 2-butanone with 6.6 ± 1.5 min to peak concentrations of 548 ± 235 ppb following ingestion of 2-butanol (40 mg). ROC areas at 5 and 10 min were 0.95 (0.86-1.00) and 1.00 (1.00-1.00). Food did not interfere. Tongue application resulted in large concentrations of 2-butanol, but not 2-butanone. A breath test to provide definitive evidence of oral medication adherence appears technically feasible.
authors.affiliation: Department of Anesthesiology, University of Florida College of Medicine, P.O. Box 100254, Gainesville, FL 32610-0254, USA.
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Morey
authors.forename: Matthew
authors.initials: M
authors.lastname: Booth
authors.forename: Scott
authors.initials: S
authors.lastname: Wasdo
authors.forename: Judith
authors.initials: J
authors.lastname: Wishin
authors.forename: Brian
authors.initials: B
authors.lastname: Quinn
authors.forename: Daniel
authors.initials: D
authors.lastname: Gonzalez
authors.forename: Hartmut
authors.initials: H
authors.lastname: Derendorf
authors.forename: Susan P
authors.initials: SP
authors.lastname: McGorray
authors.forename: Jane
authors.initials: J
authors.lastname: Simoni
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Melker
authors.forename: Donn M
authors.initials: DM
authors.lastname: Dennis
mesh_terms: D000284:Administration, Oral; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D001944:Breath Tests / Q000379:methods*; D000440:Butanols / Q000378:metabolism*; D002849:Chromatography, Gas; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D045853:Exhalation; D005240:Feasibility Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D055118:Medication Adherence
chemical_list: D000998:Antiviral Agents; D000440:Butanols; C043958:2-butanol