Effect of cimetidine on the pharmacokinetics and pharmacodynamics of chlorpheniramine and diphenhydramine in rabbits. 1996

K J Simons, and X Chen, and T G Fraser, and F E Simons
Health Sciences Clinical Research Centre, Faculties of Pharmacy, Science, and Medicine, University of Manitoba, Winnipeg, Canada.

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.

UI MeSH Term Description Entries
D007770 L-Lactate Dehydrogenase A tetrameric enzyme that, along with the coenzyme NAD+, catalyzes the interconversion of LACTATE and PYRUVATE. In vertebrates, genes for three different subunits (LDH-A, LDH-B and LDH-C) exist. Lactate Dehydrogenase,Dehydrogenase, L-Lactate,Dehydrogenase, Lactate,L Lactate Dehydrogenase
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002744 Chlorpheniramine A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than PROMETHAZINE. Chlorphenamine,Chlorprophenpyridamine,Aller-Chlor,Antihistaminico Llorens,Chlo-Amine,Chlor-100,Chlor-Trimeton,Chlor-Tripolon,Chlorpheniramine Maleate,Chlorpheniramine Tannate,Chlorpro,Chlorspan 12,Chlortab-4,Cloro-Trimeton,Efidac 24,Kloromin,Piriton,Teldrin,Maleate, Chlorpheniramine,Tannate, Chlorpheniramine
D002927 Cimetidine A histamine congener, it competitively inhibits HISTAMINE binding to HISTAMINE H2 RECEPTORS. Cimetidine has a range of pharmacological actions. It inhibits GASTRIC ACID secretion, as well as PEPSIN and GASTRIN output. Altramet,Biomet,Biomet400,Cimetidine HCl,Cimetidine Hydrochloride,Eureceptor,Histodil,N-Cyano-N'-methyl-N''-(2-(((5-methyl-1H-imidazol-4-yl)methyl)thio)ethyl)guanidine,SK&F-92334,SKF-92334,Tagamet,HCl, Cimetidine,Hydrochloride, Cimetidine,SK&F 92334,SK&F92334,SKF 92334,SKF92334
D004155 Diphenhydramine A histamine H1 antagonist used as an antiemetic, antitussive, for dermatoses and pruritus, for hypersensitivity reactions, as a hypnotic, an antiparkinson, and as an ingredient in common cold preparations. It has some undesired antimuscarinic and sedative effects. Benhydramin,Diphenylhydramin,2-Diphenylmethoxy-N,N-dimethylethylamine,Allerdryl,Benadryl,Benylin,Benzhydramine,Dimedrol,Diphenhydramine Citrate,Diphenhydramine Citrate (1:1),Diphenhydramine Hydrochloride,Diphenylhydramine,Dormin,Citrate, Diphenhydramine,Hydrochloride, Diphenhydramine
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D006634 Histamine H1 Antagonists Drugs that selectively bind to but do not activate histamine H1 receptors, thereby blocking the actions of endogenous histamine. Included here are the classical antihistaminics that antagonize or prevent the action of histamine mainly in immediate hypersensitivity. They act in the bronchi, capillaries, and some other smooth muscles, and are used to prevent or allay motion sickness, seasonal rhinitis, and allergic dermatitis and to induce somnolence. The effects of blocking central nervous system H1 receptors are not as well understood. Antihistamines, Classical,Antihistaminics, Classical,Antihistaminics, H1,Histamine H1 Antagonist,Histamine H1 Receptor Antagonist,Histamine H1 Receptor Antagonists,Histamine H1 Receptor Blockaders,Antagonists, Histamine H1,Antagonists, Histamine H1 Receptor,Antihistamines, Sedating,Blockaders, Histamine H1 Receptor,First Generation H1 Antagonists,H1 Receptor Blockaders,Histamine H1 Blockers,Receptor Blockaders, H1,Antagonist, Histamine H1,Classical Antihistamines,Classical Antihistaminics,H1 Antagonist, Histamine,H1 Antagonists, Histamine,H1 Antihistaminics,Sedating Antihistamines
D006635 Histamine H2 Antagonists Drugs that selectively bind to but do not activate histamine H2 receptors, thereby blocking the actions of histamine. Their clinically most important action is the inhibition of acid secretion in the treatment of gastrointestinal ulcers. Smooth muscle may also be affected. Some drugs in this class have strong effects in the central nervous system, but these actions are not well understood. Antihistaminics, H2,H2 Receptor Blockader,Histamine H2 Antagonist,Histamine H2 Blocker,Histamine H2 Receptor Antagonist,Histamine H2 Receptor Antagonists,Histamine H2 Receptor Blockader,Histamine H2 Receptor Blockaders,Antagonists, Histamine H2,Blockaders, Histamine H2 Receptor,H2 Receptor Blockaders,Histamine H2 Blockers,Receptor Antagonists, Histamine H2,Receptor Blockaders, H2,Antagonist, Histamine H2,Blockader, H2 Receptor,Blockaders, H2 Receptor,Blocker, Histamine H2,Blockers, Histamine H2,H2 Antagonist, Histamine,H2 Antagonists, Histamine,H2 Antihistaminics,H2 Blocker, Histamine,H2 Blockers, Histamine,Receptor Blockader, H2
D000410 Alanine Transaminase An enzyme that catalyzes the conversion of L-alanine and 2-oxoglutarate to pyruvate and L-glutamate. (From Enzyme Nomenclature, 1992) EC 2.6.1.2. Alanine Aminotransferase,Glutamic-Pyruvic Transaminase,SGPT,Alanine-2-Oxoglutarate Aminotransferase,Glutamic-Alanine Transaminase,Alanine 2 Oxoglutarate Aminotransferase,Aminotransferase, Alanine,Aminotransferase, Alanine-2-Oxoglutarate,Glutamic Alanine Transaminase,Glutamic Pyruvic Transaminase,Transaminase, Alanine,Transaminase, Glutamic-Alanine,Transaminase, Glutamic-Pyruvic

Related Publications

K J Simons, and X Chen, and T G Fraser, and F E Simons
July 1983, The American journal of cardiology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
June 1987, British journal of clinical pharmacology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
June 1988, Clinical pharmacology and therapeutics,
K J Simons, and X Chen, and T G Fraser, and F E Simons
January 1988, Journal of cardiovascular pharmacology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
March 1990, The Journal of allergy and clinical immunology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
July 1999, European journal of clinical pharmacology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
January 1983, Journal of clinical gastroenterology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
January 2000, British journal of clinical pharmacology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
January 1985, European journal of clinical pharmacology,
K J Simons, and X Chen, and T G Fraser, and F E Simons
December 1990, International journal of clinical pharmacology, therapy, and toxicology,
Copied contents to your clipboard!