Pharmacokinetics and metabolic interconversion of intravenous 4-amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide and its sulfide and sulfone metabolites in rats.

doi:10.1002/JPS.2600820705

Paper

Pharmacokinetics and metabolic interconversion of intravenous 4-amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide and its sulfide and sulfone metabolites in rats.

Published Jul 1, 1993 · B. Kuo, J. C. Poole, K. Hwang

Journal of pharmaceutical sciences

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7

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Abstract

The pharmacokinetics of a new 5-hydroxytryptamine (5HT3) receptor antagonist, 4-amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide (ML-1035, 1), and its sulfone and sulfide metabolites were examined in 12 rats. Each of these compounds (25.4 mumol/kg) was administered to rats intravenously. Their plasma concentrations were measured by high-performance liquid chromatography. These plasma data revealed that 1, a sulfoxide, underwent interconversion with its sulfide metabolite. However, no interconversion was observed between 1 and its sulfone metabolite. Examination of mean times and additional properties of the 1/sulfide metabolite system revealed that total exposure times of 1 and the sulfide metabolite were moderately and weakly, respectively, influenced by the metabolic interconversion process. However, the tissue distribution process strongly influenced the total exposure times of both compounds. The disposition of the sulfone metabolite of 1 was also strongly influenced by the tissue distribution process. In addition, < 3% of the intravenous dose of 1 or the sulfide was available to the general circulation as the sulfone metabolite.

Non-RCT

Animal Study

Study Snapshot

Intravenous 4-amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide (ML-1035) undergoes interconversion with its sulfide metabol

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

Pharmacokinetics and metabolic interconversion of intravenous 4-amino-5-chloro-2-[(methylsulfinyl)ethoxy]-N-[2-(diethylamino)ethyl] benzamide and its sulfide and sulfone metabolites in rats.

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References

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Citations

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TG100435 is a novel oral tyrosine kinase inhibitor with a more potent N-oxide metabolite, TG100855, which may significantly increase overall inhibition in animal models after oral administration.

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Determination of bioavailability and systemically available fractions of drugs undergoing reversible metabolism: application to 4-amino-5-chloro-2-[2-(methylsulfinyl)ethoxy]-N-[2- (diethylamino)ethyl]benzamide and its sulfide and sulfone metabolites in rats.

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TG100435 is a novel, orally active protein tyrosine kinase inhibitor with potential as a new cancer drug due to its potential increased tyrosine kinase inhibition in animal models.

Effects of pH and solvent on the fluorescence properties of biomedically important benzamides. Application to determination in drugs and in human urine.

Fluorescence properties of benzamides, except for alizapride, are higher at acidic pH values, making them suitable for determination in pharmaceutical preparations and human urine.