Absorption, distribution, metabolism and excretion of 2-[2-thiophenecarboxythio]-N-[dihydro-2-(3H)-thiophenone-3-yl]-propiona mide in the rat.
2-[2-Thiophenecarboxythio]-N-[dihydro-2-(3H)-thiophenone-3-y l]- propionamide (MR 889) was administered orally to rats in order to investigate its pharmacokinetics. 1-2 h after the administration, MR 889 was detected as unchanged compound in plasma only in traces whereas some catabolites, i.e. 2-thiophene carboxylic acid and its glycinate were detected with a tmax of 2 h. The thiolic component of MR 889 induced an evident and sustained increase of total sulfhydryl groups in plasma (tmax 2 h), tissues and urine. Relevant concentrations of 2-thiophene carboxylic acid were found in small intestine and gastric wall followed by liver, lungs and kidneys. The thiolic component also increased, mainly in liver and lungs followed by small intestine and gastric wall. Homocysteine thiolactone S-methyl thiolactamide was identified as a minor metabolite of MR 889.
Gentili
P
P
Medea Research s.r.l., Milan, Italy.
Pelloso
R
R
La Rosa
C
C
Galzigna
L
L
Lucarelli
C
C
D000284:Administration, Oral; D000818:Animals; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005243:Feces / Q000737:chemistry; D007274:Injections, Intraperitoneal; D007408:Intestinal Absorption; D008297:Male; D011480:Protease Inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000097:blood; D013876:Thiophenes / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D011480:Protease Inhibitors; D013438:Sulfhydryl Compounds; D013876:Thiophenes; C062051:midesteine