Pharmacokinetics and metabolism of N-(2-hydroxyethyl)-2,5-[14C]-pyrrolidine (HEP, Epolamine) in male healthy volunteers.
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.
Giachetti
C
C
Istituto di Ricerche Biomediche A. Marxer, RBM SpA, Colleretto Giacosa, Turin, Italy.
Assandri
A
A
Mautone
G
G
Tajana
E
E
Palumbo
B
B
Palumbo
R
R
D000328:Adult; D002250:Carbon Radioisotopes; D005243:Feces / Q000737:chemistry; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D011759:Pyrrolidines / Q000097:blood / Q000378:metabolism / Q000493:pharmacokinetics* / Q000652:urine
D002250:Carbon Radioisotopes; D011759:Pyrrolidines; C104862:epolamine