Pharmacokinetics and metabolism of N-(2-hydroxyethyl)-2,5-[14C]-pyrrolidine (HEP, Epolamine) in male healthy volunteers

• Published in: European journal of drug metabolism and pharmacokinetics 1996-07, Vol.21 (3), p.261-268
• Main Authors: GIACHETTI, C, ASSANDRI, A, MAUTONE, G, TAJANA, E, PALUMBO, B, PALUMBO, R
• Format: Article
• Language: English
• Subjects: Adult; Biological and medical sciences; Carbon Radioisotopes; Feces - chemistry; Gas Chromatography-Mass Spectrometry; General pharmacology; Humans; Male; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Pyrrolidines - blood; Pyrrolidines - metabolism; Pyrrolidines - pharmacokinetics; Pyrrolidines - urine
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/bf03189724

N-(2-hydroxyethyl)-pyrrolidine (HEP, Epolamine) is a strong base used to salify organic acids of pharmaceutical interest in order to improve their solubility in water. Diclofenac-HEP (Flector) is the first example of an epolamine salt of a drug. In this study, [14C]-HEP was administered by oral route (300 mg, about 50 microCi/subject) to 3 volunteers with the aim to investigate its plasma profile and to calculate the relevant pharmacokinetic parameters. The experimental data correlated with a two-compartment pharmacokinetic model. Total radioactivity in urine and faeces was also measured. The radioactivity was excreted preferentially by the faecal route (about 65% of the dose administered in the 0-72 h collection interval). Urinary excretion accounted for about 30% of the dose and occurred very rapidly (about 22% of the dose was in the 0-8 h collection interval). Metabolic investigations were carried out on urine samples. TLC analysis with radioscan detector indicated a main radioactive zone, accounting for about 98% of the radioactivity in the plate. After scraping off and purification of the radioactive areas, the compound isolated (Met I) was analysed by gas chromatography-mass spectrometry with electron-impact ionization process. The structure of the metabolite was postulated to be pyrrolidine N-oxide.