title: Effect of cimetidine on the pharmacokinetics and pharmacodynamics of chlorpheniramine and diphenhydramine in rabbits.
abstract: OBJECTIVE
  The effects of concomitant administration of the H2-receptor antagonist cimetidine on the pharmacokinetics and pharmacodynamics of the H1-receptor antagonists chlorpheniramine and diphenhydramine were studied in rabbits.
  
  
  METHODS
  A single dose of chlorpheniramine 10 mg (Group A) or diphenhydramine 10 mg (Group B) was given intravenously on three different study days as follows: 2 weeks before cimetidine administration, after giving cimetidine 100 mg/kg intravenously every 12 hours for one week, and two weeks after discontinuing the cimetidine. Serum chlorpheniramine and diphenhydramine concentrations were measured by HPLC. Histamine H1-blockade was assessed by measuring suppression of the histamine-induced wheals in the skin.
  
  
  RESULTS
  The chlorpheniramine and diphenhydramine terminal elimination half-life values and area under the curve values were significantly increased, and the systemic clearance rates were significantly decreased, during concomitant administration of cimetidine. For each H1-receptor antagonist, pharmacokinetic parameters were similar before cimetidine was co-administered and two weeks after cimetidine was discontinued. Wheal suppression produced by chlorpheniramine or diphenhydramine was increased and prolonged when cimetidine was administered concomitantly.
  
  
  CONCLUSIONS
  Any enhanced peripheral H1-blockade observed could be attributed, at least in part, to a pharmacokinetic interaction.
authors.affiliation: Health Sciences Clinical Research Centre, Faculties of Pharmacy, Science, and Medicine, University of Manitoba, Winnipeg, Canada.
authors.forename: K J
authors.initials: KJ
authors.lastname: Simons
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: T G
authors.initials: TG
authors.lastname: Fraser
authors.forename: F E
authors.initials: FE
authors.lastname: Simons
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002744:Chlorpheniramine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology*; D004155:Diphenhydramine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004347:Drug Interactions; D006634:Histamine H1 Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000502:physiology; D011817:Rabbits
chemical_list: D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D002744:Chlorpheniramine; D002927:Cimetidine; D004155:Diphenhydramine; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase