Pharmacokinetics

Absorption Distribution Metabolism Excretion Special Population (N/A) Other Details

 

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 below.

Dose 5 mg 10 mg 15 mg
Number of patients 10 10 10
Cmax (pg/mL) 186.8±87.1 386.4±215.4 389.7±103.6
AUC0-∞ (pg•h/mL) 837.8±572.9 1272.5±656.2 1632.2±475.8
Tmax (h) 1.8±1.6 1.9±1.6 1.8±0.6
t1/2 (h) 3.3±3.1 2.5±1.5 3.2±1.5

 

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 below.

Parameter 5 mg 14C-elobixibat
Cmax (nmol/L) 0.5±0.3
AUC0-∞ (nmol•h/L) 1.2±0.4 (n = 3)
Tmax (h)* 0.8 (0.5‒2.0)
t1/2 (h) 0.8±0.2 (n = 3)

 

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

  1. 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.
  2. 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.

 

Special Population

N/A


 

Other details

Drug-Drug Interaction

  1. 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.
  2. 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 AUC0-t and Cmax 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. AUC0-t and Cmax 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 AUC0-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. Cmax and AUC0-∞ under fed condition were approximately 20 to 30% of those under fasting one.