Pharmacokinetics of Freddie

The rapid absorption of repaglinide through gastrointestinal tract leads to a rapid increase in blood concentration. The blood concentration reached its peak within 65438 0 hours after taking the drug. Then the plasma concentration decreased rapidly and was eliminated within 4 ~ 6 hours. The plasma half-life is about 65438 0 hours. The binding rate of repaglinide to human plasma protein is more than 98%. Repaglinide is almost completely metabolized, and the metabolites have no clinical hypoglycemic effect. Repaglinide and its metabolites are mainly excreted from bile, and a small part (less than 8%) of its metabolites are excreted from urine. Feces contain less than 2% of the original drug. According to foreign literatures, the steady-state pharmacokinetics of type 2 diabetic patients with normal renal function (CRCL) of 80 ml/min, mild and moderate renal impairment (CRCL = 40 ~ 80 ml/min) and severe renal impairment (CRCL = 20 ~ 40 ml/min) were compared. AUC and Cmax between patients with normal renal function and patients with mild to moderate renal impairment are similar (the average values are 56.7 ng/ml * hr and 57.2 ng/ml * HR； respectively; 37.5 ng/ml and 37.7 ng/ml). AUC and cmax of patients with severe renal insufficiency increased significantly (98.0 ng/ml * hr and 50.7 ng/ml respectively), but this study only showed a weak correlation between repaglinide concentration and creatinine clearance rate (CrCl). Patients with mild and moderate renal impairment do not need to adjust the initial dose. However, for type 2 diabetic patients with severe renal function damage, the initial dose should be set at 0.5mg, and the dose should be carefully adjusted in the future. The study of renal failure patients with creatinine clearance less than 20 ml/min and requiring hemodialysis has not been carried out. According to foreign literature, according to Child-Pugh classification and caffeine clearance rate, single-dose and open-label studies were conducted in 12 healthy subjects and 12 patients with chronic liver disease. Compared with healthy subjects, patients with moderate and severe liver injury have higher overall blood drug concentration and free repaglinide concentration and longer duration (AUC of healthy subjects: 91.6 ng/ml * hr; AUC of patients with chronic liver disease: 368.9 ng/ml * hr; Healthy subjects (Cmax: 46.7 ng/ml; Cmax of patients with chronic liver disease:105.4 ng/ml). There is a statistical correlation between AUC and caffeine clearance rate. No difference in blood glucose profile was observed in the patient group. The plasma concentrations of repaglinide and related metabolites in patients with liver injury are higher than those in healthy subjects under the condition of receiving ordinary dose. Therefore, repaglinide should be used with caution in patients with impaired liver function. The interval of dose adjustment should be longer to accurately evaluate the drug treatment response.