Abstract |
1. In 24 h, male rats excreted in urine 1% of an intra-gastric 100 mg/kg dose of 4-amino-5-ethyl-3-[4-14C]thiophenecarboxylic acid methyl ester hydrochloride (I) as unchanged I and 59% as 4-amino-5-ethyl-3-thiophenecarboxylic acid (II), mostly conjugated. 2. In rats dosed intra-duodenally with I (50 mg/kg), little I was found in the systemic circulation (less than 2 micrograms/ml) but high concentrations (26 micrograms/ml) were present at five minutes in portal plasma. At five minutes, II was found at 89 and 93 micrograms/ml in systemic and portal plasma, respectively. First-pass ester hydrolysis by the duodenum and liver may explain the near absence of I and the high concentrations of II in systemic plasma. 3. Dogs which received 30 mg/kg 14C-I intra-gastrically, excreted 0.3% I, 30.8% II and 6.8% as 5-ethyl-4-(methylamino)-3-thiophenecarboxylic acid (III), the N-methyl derivative of II. 4. Dogs which received approximately equivalent intra-venous or intra-gastric doses of non-radioactive I and II had high plasma concentrations of II but only small concentrations of I. Plasma concentrations of II after intra-gastric doses of non-radioactive I or II were similar, indicating that both compounds are pharmacokinetically equivalent. I may be a prodrug of II.
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Authors | F J Leinweber, A J Szuna, A C Loh, T H Williams, G J Sasso, I Bekersky, E Baggiolini, J Triscari |
Journal | Xenobiotica; the fate of foreign compounds in biological systems
(Xenobiotica)
Vol. 17
Issue 12
Pg. 1405-14
(Dec 1987)
ISSN: 0049-8254 [Print] England |
PMID | 3439191
(Publication Type: Journal Article)
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Chemical References |
- Fatty Acids
- Thiophenes
- Ro 22-0654
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Topics |
- Animals
- Chromatography, High Pressure Liquid
- Chromatography, Thin Layer
- Dogs
- Fatty Acids
(biosynthesis)
- Feces
(analysis)
- Female
- Liver
(cytology, metabolism)
- Magnetic Resonance Spectroscopy
- Male
- Mass Spectrometry
- Rats
- Rats, Inbred Strains
- Species Specificity
- Thiophenes
(metabolism, pharmacology, urine)
- Time Factors
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