Goofice Mechanism of Action

Pharmacology: Mechanism of Action: Elobixibat inhibits bile acid reabsorption via ileal bile acid transporter (IBAT) expressed on the epithelial cells of the terminal ileum and thereby increases the amount of bile acid passing into the large intestinal lumen. Bile acid promotes the secretion of water and electrolytes into the large intestinal lumen and enhances the colonic motility. Therefore, Elobixibat (GOOFICE) induces the therapeutic effect on constipation.
Pharmacokinetics: Absorption: A single oral dose of Elobixibat (GOOFICE) 5 mg, 10 mg or 15 mg was administered to patients with chronic constipation before breakfast and the pharmacokinetic parameters were noted as follows. (See Table 1.)

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A single oral dose of ¹⁴C-elobixibat 5 mg (approx. 2.75 MBq) was administered to healthy adult male subjects (n=6) before breakfast and the pharmacokinetic parameters were noted as follows. (See Table 2.)

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Distribution: In vitro human plasma protein binding rate of elobixibat was in excess of 99% with human blood to plasma concentration ratio less than 5%.
Metabolism: No metabolites were observed in plasma of healthy adult male subjects (n=6) following a single oral dose of ¹⁴C-elobixibat 5 mg (approx. 2.75 MBq). Unchanged and monohydroxy forms of elobixibat were found in feces pooled over 24 to 48 hours post-dose, while the percentages of radioactivity were 96.06% and 3.16%, respectively, indicating that the majority was unchanged form.
Excretion: When a single oral dose of Elobixibat (GOOFICE) was administered to patients with chronic constipation under fasting conditions, the cumulative urine drug excretion rate up to 144 hours post-dose was approximately 0.01% of the amount of dose, indicating that drug excretion into urine was almost absent.
When a single oral dose of ¹⁴C-elobixibat 5 mg (approx. 2.75 MBq) was administered to healthy adult male subjects (n=6), 103.1% of radioactivity dosed was excreted in feces while 0.00 to 0.02% excreted in urine up to 144 hours post-dose.
Drug-Drug Interaction: IC₅₀ of elobixibat towards digoxin (P-glycoprotein substrate) transport was 2.65 μmol/L in Caco-2 cells, indicating the inhibitory effect of elobixibat on P-glycoprotein.
In healthy adult male and female subjects (n=25), Elobixibat (GOOFICE) 10 mg was orally administered once daily for 5 days with coadministration of both dabigatran etexilate 150 mg/dose/day on Day 1 and midazolam 2 mg/dose/day on Day 1 and Day 5 to compare with monoadministration of each drug. The results showed that AUC_0-t and C_max of dabigatran (P-glycoprotein substrate) were 1.17 fold greater (90% confidence interval: 1.00-1.36) and 1.13 fold greater (90% confidence interval: 0.96-1.33), respectively, compared with those under monoadministration and both the upper limit of 90% confidence intervals were above 1.25 as the reference value. AUC_0-t and C_max of midazolam on Day 5 were 0.78-fold greater (90% confidence interval: 0.73-0.83) and 0.94-fold greater (90% confidence interval: 0.87-1.01), respectively, compared with those under monoadministration and the lower limit of 90% confidence intervals of AUC_0-t was below 0.80 as the reference value.
Food Effects: In patients with chronic constipation (n=60), the effect of food intake on pharmacokinetics was evaluated following a single oral dose of Elobixibat (GOOFICE) in a crossover design. C_max and AUC_0-∞ under fed condition were approximately 20 to 30% of those under fasting one.
Toxicology: Effect on Constipation Induced by Loperamide in Rats: In rats of loperamide-induced constipation model, a single oral administration of elobixibat demonstrated the effect of improving constipation.