Premium
Administration of H 1 and H 2 Antagonists for Chemoprophylaxis: A Double‐Blind, Placebo‐Controlled Study in Healthy Volunteers
Author(s) -
Doenicke Alfred,
Moss Jonathan,
Toledano Alicia,
Hoernecke Rainer,
Lorenz Wilfried,
Ostwald Philipp
Publication year - 1997
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1002/j.1552-4604.1997.tb04772.x
Subject(s) - histamine , antihistamine , medicine , placebo , cimetidine , chemoprophylaxis , anesthesia , erythema , pharmacology , histamine h1 receptor , histamine h1 antagonists , terfenadine , antagonist , immunology , receptor , pathology , alternative medicine
A double‐blind, placebo‐controlled trial was performed to establish the duration of action of antihistamines and their ability to attenuate the adverse effects associated with histamine release. Thirty volunteers were assigned randomly to receive either placebo or a combination of the H 1 blocker dimetindene maleate (0.1 mg/kg) and the H 2 blocker cimetidine (5 mg/kg). A bolus dose of histamine (450 ng/kg) was given 15 minutes after antihistamine or placebo treatment and repeated after 2, 4, and 6 hours. Cardiovascular variables, plasma histamine levels, cutaneous manifestations, and objective and subjective signs and symptoms associated with histamine release were determined before and after each histamine injection. Although many of the signs of histamine release, including erythema and metallic taste, could be attenuated effectively for 6 hours with antihistamine treatment, the protection against histamine‐induced flush and headache diminished after 2 hours. Statistically significant protection against histamine‐mediated tachycardia persisted for only 2 hours. Antihistamine treatment significantly reduced the increase in plasma histamine levels after the first histamine injection but did not alter the levels after subsequent histamine injections. The currently recommended administration regimen for prophylaxis with antihistamines is insufficient to prevent histamine‐mediated side effects, and additional doses may be required after 4 hours to achieve appropriate chemoprophylaxis.