alexa Pharmacokinetics of amezinium in rat and dog.
Pharmaceutical Sciences

Pharmaceutical Sciences

Pharmaceutica Analytica Acta

Author(s): Traut M, Brode E, Neumann B, Kummer H

Abstract Share this page

Abstract Using 14C-labelled 4-amino-6-methoxy-1-phenyl-pyridazinium methyl sulfate (ameziniummetilsulfate, LU 1631, Regulton), briefly called amezinium, the time course of plasma level in the rat and of blood level and renal excretion rate in the dog has been followed. The distribution of radioactivity in the organism was investigated by autoradiography of whole-animal sections and by quantitative radioactivity determinations in rat tissue as well as by in vitro experiments. From the results we draw the following conclusions: 1. In the two species investigated here, amezinium is almost completely absorbed after enteral administration. In the rat the absorption proceeds with a half-life of 11 min, after a lag phase of 6 min. In the dog, the lag phase is 30-40 min, after which the compound is absorbed with a half-life of 30 min or less. The small intestine appears to be the site of absorption. 2. Amezinium has a high affinity for tissues. Its transport through the cell membrane, in the case of sympathetic neurons and probably also in the case of other chromaffin cells, is mediated by the noradrenaline carrier; in other tissues, for example the liver, a different active transport mechanism, as yet not elucidated, is operating. The placenta and blood-brain barrier are passed only slightly, if at all. In rat blood amezinium distributes between erythrocytes and plasma with a ratio of 2.7:1; the proportion bound to plasma proteins is about 20\%. 3. In the rat amezinium is eliminated from the circulation to the extent of about 3/4 by biotransformation; on enteral administration, about 80\% is trapped by first-pass metabolism. In the dog biotransformation accounting for about 40\% of the elimination is relatively unimportant; the first-pass metabolism is virtually negligible. 4. Amezinium is eliminated by rats about equally with urine and bile, whilst in the dog the predominant proportion is excreted renally. From plasma level curves the terminal half-life t 1/2 (beta) in the rat was found to be 17 h and 21 h after i.v. and p.o. administration, respectively; blood level data and urinary excretion data in the case of the dog gave 5 1/2 (beta) values between 11 h and 20 h. 5. Renal clearance of amezinium in the dog is not constant: initially it is several times greater than the glomerular filtration rate (GFR) decreasing subsequently to about the same magnitude or even below the GFR.
This article was published in Arzneimittelforschung and referenced in Pharmaceutica Analytica Acta

Relevant Expert PPTs

Relevant Speaker PPTs

Recommended Conferences

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords