title: ABH gel is not absorbed from the skin of normal volunteers.
abstract: BACKGROUND
  Lorazepam (Ativan(®)), diphenhydramine (Benadryl(®)), haloperidol (Haldol(®)) (ABH) topical gel is currently widely used for nausea in hospice because of perceived efficacy and low cost and has been suggested for cancer chemotherapy. However, there are no studies of absorption, a prerequisite for effectiveness. We completed this study to establish whether ABH gel drugs are absorbed, as a prerequisite to effectiveness.
  
  
  METHODS
  Ten healthy volunteers, aged 25 to 58 years (mean 37 years), two African Americans and eight Caucasian Americans, applied the standard 1.0 mL dose (2mg of lorazepam, 25mg of diphenhydramine, and 2mg of haloperidol in a pluronic lecithin organogel), rubbed on the volar surface of the wrists by the subject.
  
  
  METHODS
  Blood samples were obtained at 0, 30, 60, 90, 120, 180, and 240 minutes. Plasma concentrations were analyzed by liquid chromatography-tandem mass spectrometry using deuterated internal standards for each drug.
  
  
  RESULTS
  No lorazepam or haloperidol was detected in any sample from any of the 10 volunteers down to a level of 0.05 ng/mL. Diphenhydramine was found in multiple plasma samples at concentrations >0.05 ng/mL in three patients, with the highest concentration of 0.30 ng/mL in one person at 240 minutes. Overall, five of 10 patients exhibited detectable diphenhydramine in one or more samples, supporting limited absorption. No subject noted any side effects.
  
  
  CONCLUSIONS
  As commonly used, none of the lorazepam, haloperidol, or diphenhydramine in ABH gel is absorbed in sufficient quantities to be effective in the treatment of nausea and vomiting. Diphenhydramine is erratically absorbed at subtherapeutic levels. The efficacy of ABH gel should be confirmed in randomized trials before its use is recommended.
authors.affiliation: Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-0005, USA. tsmit136@jhmi.edu
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Smith
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Ritter
authors.forename: Justin L
authors.initials: JL
authors.lastname: Poklis
authors.forename: Devon
authors.initials: D
authors.lastname: Fletcher
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Coyne
authors.forename: Patricia
authors.initials: P
authors.lastname: Dodson
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Parker
mesh_terms: D000042:Absorption; D000279:Administration, Cutaneous; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004155:Diphenhydramine / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006220:Haloperidol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008140:Lorazepam / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D012867:Skin / Q000378:metabolism*
chemical_list: D000932:Antiemetics; D004155:Diphenhydramine; D006220:Haloperidol; D008140:Lorazepam