Disposition of bemitradine, a Renal Vasodilator and Diuretic, in Man

Abstract

1. ¹⁴C-Bemitradine (50 mg) was rapidly and efficiently absorbed (β89%) in man following a single oral dose, as a solution in gelatine capsules. Peak ¹⁴Clevels of 895 ± 154 ng equiv./ml (mean ± S.E.M.) were reached within 2h, and declined with half-lives of 1·07 ± 0·25 and 13·0± 5·6h.

2. No bemitradine was detected in plasma, but peak concn. (124±29ng/ml) of its desethyl metabolite were reached at 1·05±0·28h, and declined with a half-life of 1·32±0·08h.

3. Desethylbemitradine was rapidly metabolized to its ether glucuronide, a phenol and a dihydrodiol which were also present as glucuronide conjugates. The glucuronides were the major compounds in plasma from 2h after drug administration.

4. Excretion in 5 days amounted to 88·8±2·3% and 10·4±2·1% dose in urine and faeces respectively. No bemitradine or desethylbemitradine were excreted unchanged. 8-(2-Hydroxyethyl)-7-(3,4-dihydroxycyclohexa-l,5-dienyl)-l,2,4-triazolo-l,5c-pyrimidine-5-amine (E; 17% dose); 8-(2-hydroxyethyl)-7-(4-hydroxyphenyl)-l,2,4-triazolo-1.5c-pyrimidine-5-amine (F; 4% dose), their glucuronides (A, 19% dose and B, 6% dose respectively), desethylbemitradine glucuronide (D, 25% dose) and an unidentified metabolite (C, 12% dose) were excreted in urine. Compound F was the major faecal metabolite.