Absorb

After oral administration, ezetimibe is rapidly absorbed and widely combined into phenolic glucuronide (ezetimibe-glucuronide) with pharmacological activity. The ezetimibe-glucuronide conjugate reaches the average peak plasma concentration (Cmax) within 1 to 2 hours after taking the drug, while the average peak plasma concentration of ezetimibe appears at 4 to 12 hours. Since ezetimibe is insoluble in the water-based medium for injection, its absolute bioavailability cannot be measured.

Taking 10mg ezetimibe tablets together with food (high-fat or fat-free diet) does not affect its oral bioavailability. This product can be taken with food or separately.

Distributed

The binding rates of ezetimibe and ezetimibe-glucuronide conjugate to plasma protein were 99.7% and 88-92%, respectively.

Metabolism

Ezetimibe binds to glucuronide (phase II reaction) mainly in the small intestine and liver, and is then excreted by the bile and kidneys. Among all the species studied, a very small amount of ezetimibe undergoes oxidative metabolism (phase I reaction). Ezetimibe and ezetimibe-glucuronide conjugates are the main drug derivatives detected in plasma, accounting for 10-20% and 80-90% of the total drug concentration in plasma, respectively. The clearance of ezetimibe and ezetimibe-glucuronide conjugate in plasma is relatively slow, suggesting significant enterohepatic circulation. The half-life of ezetimibe and ezetimibe-glucuronide conjugate is approximately 22 hours.

Clear

After subjects took 14C ezetimibe (20mg) orally, the total ezetimibe accounted for about 93% of the total plasma radioactivity. During the 10-day collection period, approximately 78% and 11% of the taken radioactivity can be recovered from feces and urine, respectively. After 48 hours, no radioactivity was detected in the plasma.

Liver insufficiency

Patients with mild hepatic insufficiency (Child-Pugh score 5 or 6) took a single dose of ezetimibe 10 mg, the total area under the ezetimibe curve (AUC) increased by about 1.7 times compared with the normal population. In a 14-day multiple-dose study of patients with moderate hepatic insufficiency (Child-Pugh score 7-9), the patients took 10mg of this product every day, and the total amount of ezetimibe on the 1st and 14th day The area under the curve is 4 times higher than that of the normal population. Patients with mild hepatic insufficiency do not need to adjust the medication dose. In view of the fact that the effect of increased ezetimibe exposure on patients with moderate and severe hepatic insufficiency (Child-Pugh score>9) is not yet clear, ezetimibe is not recommended for these patients. (See Contraindications and Precautions, Liver Insufficiency)

Renal insufficiency

In patients with severe renal insufficiency (n=8; average CrCl≤30mL/min/1.73m2), after a single dose of 10 mg ezetimibe, the total area under the ezetimibe curve increased by 1.5 times compared with the normal population (n=9) . This result has no clinical significance. Therefore, there is no need to adjust the dose in patients with renal impairment.

But one patient in the study (who received a kidney transplant and received multiple drugs, including cyclosporin) had a total ezetimibe exposure that was 12 times higher than the normal population.

Gender

The total plasma concentration of ezetimibe in women is slightly higher than that in men (increased value <20%). The safety of medication and the degree of LDL-C reduction after medication were similar in male and female patients. Therefore, there is no need to adjust the dose according to gender.

Race

According to the pharmacokinetic meta-analysis, there is no difference in pharmacokinetics between black people and white people.