Disposition of bemitradine, a renal vasodilator and diuretic, in man.
1. 14C-Bemitradine (50 mg) was rapidly and efficiently absorbed (approximately 89%) in man following a single oral dose, as a solution in gelatine capsules. Peak 14C levels of 895 +/- 154 ng equiv./ml (mean +/- S.E.M.) were reached within 2 h, 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 +/- 29 ng/ml) of its desethyl metabolite were reached at 1.05 +/- 0.28 h, and declined with a half-life of 1.32 +/- 0.08 h. 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 2 h 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-1,5-dienyl)-1,2,4-triazolo-1,5c-pyrimidin e-5-amine (E; 17% dose); 8-(2-hydroxyethyl)-7-(4-hydroxyphenyl)-1,2,4-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.
Walls
C M
CM
G. D. Searle & Co. Ltd., High Wycombe, Bucks, UK.
Gray
A
A
Vose
C W
CW
Robinson
Y
Y
Lopez
N
N
Brownsill
R D
RD
Steiner
J A
JA
D000042:Absorption; D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D004232:Diuretics / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D012079:Renal Circulation / Q000187:drug effects; D014230:Triazoles / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
D004232:Diuretics; D005965:Glucuronates; D011743:Pyrimidines; D014230:Triazoles; D014665:Vasodilator Agents; C059265:bemitradine