[Absorption, distribution, excretion and metabolism of 4-carbomethoxythiazolidine chlorohydrate. Biochemical experimental study in the rat].
A biochemical-metabolic study has been conducted on TCM (4-carbomethoxythiazolidin hydrochloride) in rats, utilising a product traced with 14C. An in-vitro test has demonstrated that TCM is hydrolised by endogenous esterases to thiazolidincarboxylic acid, into the following decreasing order of activity: kidneys, lungs, plasma, liver, intestinal content and mucosa. Upon oral administration, TCM proved to have a good and rapid absorption and distribution level in the organs. In the beginning the liver and the kidneys have displayed higher concentrations with respect to the lungs; after 8 hours, however, the latter have displayed slightly lower concentrations than before, which were not very far from the liver's and kidneys'. TCM has been mainly eliminated through the urines (56.9% in 24 hours) and less through the feces (6.7% in the same period of time). By means of a thin-layer chromatography analysis and a mass-spectrometry it has been possible to study the metabolism of TCM. The results of both in-vitro and in-vivo tests have demonstrated that TCM is hydrolised to thiazolidin-carboxylic acid, which, in its turn, is transformed into cysteine. This last transformation does mainly occur in the liver, but significantly in the lungs as well. TCM is absorbed in part as such and in part as thiazolidincarboxylic acid. As no methyl-cysteinate has been traced, it has been assumed that the hydrolysis of the ester bond was a kinetically quicker event than the heterocycle opening.
Esposito
G
G
Facoltà di Farmacia, Università di Milano.
Cattaneo
C
C
Rizzo
A
A
Berra
B
B
D000818:Animals; D005100:Expectorants / Q000378:metabolism / Q000493:pharmacokinetics*; D066298:In Vitro Techniques; D007408:Intestinal Absorption; D051381:Rats; D013844:Thiazoles / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D005100:Expectorants; D013844:Thiazoles; C070586:4-carbomethoxythiazoline
Assorbimento, distribuzione, escrezione e metabolismo della 4-carbometossitiazolidina cloridrato. Studio biochimico sperimentale nel ratto.