Urinary excretion of the 1,4-dihydropyridine calcium antagonist VULM 993 and its metabolites in the rat.
After oral dose of the 1,4-dihydropyridine calcium antagonist 14C-VULM 993 (50 mg/kg) a mean of 44.5% of the administered radioactivity was excreted via urine during the first 72 hours. Using an extractive fractionation procedure, the urinary metabolites were classified on the basis of their polarity and acidic/basic properties. Approx. 40% of total urine metabolites were found to be polar, non-extractable compounds--mostly glucuronide/sulphate conjucates. About one half of all urine metabolites were shown to possess overall acidic nature. G.l.c.-m.s. and t.l.c.-m.s. analyses of urine extracts revealed the presence of only minor amounts of the parent drug toghether with six metabolites identified as products of 1,4-dioxaspiro[4,4]nonane moiety cleavage, hydrolysis of one or both ester side functions also combined with 1,4-dihydropiridine nucleus dehydrogenation. Technique of thin-layer radio-chromatography was used to quantify urinary excretion rates of the parent drug and the established metabolites.
Stefek
M
M
Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
Faberova
V
V
Musil
S
S
Kakalik
I
I
D000818:Animals; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000652:urine*; D002855:Chromatography, Thin Layer; D008401:Gas Chromatography-Mass Spectrometry; D008297:Male; D008956:Models, Chemical; D011725:Pyridines / Q000378:metabolism / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D013141:Spiro Compounds / Q000378:metabolism / Q000652:urine*
D002121:Calcium Channel Blockers; D011725:Pyridines; D013141:Spiro Compounds; C405569:VULM 993