Metabolism and excretion of a new 5-lipoxygenase inhibitor in rats, guinea-pigs, beagles and rhesus monkeys.
1. The 5-lipoxygenase inhibitor (I), a substituted benzothiazole is metabolized mainly by glucuronide and/or sulphate conjugation in rat, guinea-pig, beagle and rhesus monkey. Glucuronidation is the major pathway, and sulphation is more extensive in rat and beagle than in guinea-pig and rhesus monkey. 2. After a single oral dosing of 14C-I (10 mg/kg), more than 96% of the dose was excreted in 7 days in all four species, however there is species difference in urinary excretion, which was 2.8 +/- 0.3% in rat, 46.9 +/- 1.6% in guinea-pig, 2.6% in beagle and 68.2% in rhesus monkey. 3. After a single i.v. dose of 14C-I to bile duct-cannulated rats and guinea pigs, bile was a major route of elimination, and in rats the ratio of glucuronide to sulphate in excreta increased from 0.71 +/- 0.01 to 0.93 +/- 0.05 as the dose was increased from 0.2 to 20 mg/kg.
Yoshimura
T
T
Tsukuba Research Laboratories, Eisai Co., Ltd., Ibaraki, Japan.
Tanaka
S
S
Sakurai
H
H
Nagai
Y
Y
Yamada
K
K
Katayama
S
S
Abe
S
S
Yamatsu
I
I
D000818:Animals; D001646:Bile / Q000378:metabolism; D002250:Carbon Radioisotopes; D004285:Dogs; D006168:Guinea Pigs; D016859:Lipoxygenase Inhibitors / Q000493:pharmacokinetics*; D008253:Macaca mulatta; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013844:Thiazoles / Q000737:chemistry / Q000493:pharmacokinetics*
D002250:Carbon Radioisotopes; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; C064507:E 6080