1991
DOI: 10.3109/00498259109039502
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Metabolism and excretion of a new 5-lipoxygenase inhibitor in rats, guinea-pigs, beagles and rhesus monkeys

Abstract: 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… Show more

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Cited by 4 publications
(3 citation statements)
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“…Similarly, the glucuronide of a lipoxygenase inhibitor (E6080) has been reported as a compound exhibiting a species difference in excretion route (Yoshimura et al 1991). Urinary excretion of the E6080 glucuronide accounted for 68.4% of dose in monkeys, but only 0.5% of dose in rats, in which the glucuronide was predominantly excreted in bile (42.5% of dose).…”
Section: Discussionmentioning
confidence: 98%
See 1 more Smart Citation
“…Similarly, the glucuronide of a lipoxygenase inhibitor (E6080) has been reported as a compound exhibiting a species difference in excretion route (Yoshimura et al 1991). Urinary excretion of the E6080 glucuronide accounted for 68.4% of dose in monkeys, but only 0.5% of dose in rats, in which the glucuronide was predominantly excreted in bile (42.5% of dose).…”
Section: Discussionmentioning
confidence: 98%
“…The lack of dose proportionality in AUC is likely due to reabsorption of KW-4490 excreted into bile from the intestinal tract. When CL R was compared with glomerular filtration rate (GFR) of unbound KW-4490, estimated from creatinine clearance data (rats ¼ 0.432 and monkeys ¼ 0.120-0.142 l h À1 kg À1 ) (Yoshimura et al 1991) and f p of KW-4490, CL R in rats was less than f p ÁGFR (0.159 l h À1 kg À1 ), whereas CL R in monkeys was more than f p ÁGFR (0.00912-0.0108 l h À1 kg À1 ). These results indicate that renal tubular secretion contributes greatly to urinary excretion of KW-4490 in monkeys, but that large amounts of excreted KW-4490 are reabsorbed across the renal tubules in rats.…”
Section: Discussionmentioning
confidence: 99%
“…This species difference in excretion may reflect differences in urinary metabolite composition. Species variations have been reported in the threshold molecular weight for biliary excretion [4,5] and may contribute to species differences in the main excretion route. 14 C-NS-7 showed no marked species difference for serum protein binding in the rats, dogs, monkeys and humans, and specific binding to any of the representative human serum proteins.…”
Section: Discussionmentioning
confidence: 99%