Special Populations
Geriatric Patients: Repaglinide's elimination half-life was longer in a study of 11 elderly NIDDM patients (patients over 65 years old), with a mean value of 7.2 hours compared to 3.3 hours in patients between the ages of 18 and 54. In this study, the geriatric patients' CL/F was decreased and their V/F was raised. The dosage for elderly NIDDM patients does not need to be changed.
Hepatic Impairment: After a single 0.5 mg oral dose, the pharmacokinetics of repaglinide were assessed in 8 subjects with mild (n = 4) and moderate (n = 4) hepatic impairment. Subjects with mild hepatic impairment had Cmax and AUC that were about 2-fold higher than those in healthy subjects, but there was no discernible change in Cmax. Cmax was three times higher, Tmax was prolonged, and AUC was five times higher in subjects with moderate hepatic impairment than in healthy subjects. Both mild and moderate hepatic impairment led to a 50% reduction in the mean apparent clearance (CL/F).
For patients with mild hepatic impairment, there is no need to change the dosage. The starting dose for patients with moderate hepatic impairment should be 0.5 mg once daily.
Renal Impairment: As renal function declined, there was a decrease in the apparent clearance (CL/F) of repaglinide and an increase in the AUC in a study of 8 NIDDM patients with varying levels of renal function (creatinine clearance ranging from 22 to 78 mL/min).
For patients with mild to moderate renal impairment (creatinine clearance 30 mL/min), there is no need to change the dosage. starting dose should be 0.5 mg once daily for patients with severe renal impairment (creatinine clearance 30 mL/min). Repaglinide dosage adjustments should be made in accordance with the patient's response, which should be closely monitored.
Drug Interactions: In vitro research indicates that repaglinide is a cytochrome P450 3A4 (CYP3A4) substrate. Ketoconazole, a CYP3A4 inhibitor, was administered concurrently with repaglinide, which caused its AUC and Cmax to increase by twofold. The pharmacokinetics of repaglinide were unaffected when it was co-administered with gemfibrozil, another CYP3A4 inhibitor.
The pharmacokinetics of repaglinide were unaffected by the coadministration of repaglinide (0.5 mg single dose) and the gastric acid secretion inhibitor cimetidine (800 mg single dose).
Repaglinide is not an inhibitor of the cytochrome P450 isozymes 1A2, 2C9, 2C19, 2D6, or 3A4 according to in vitro data.
Repaglinide does not appear to induce the cytochrome P450 isozymes 1A2, 2B1, 2C9, or 3A4 according to in vitro data.
Following single-dose administration of metformin hydrochloride (500 mg) and repaglinide (0.5 mg) to healthy volunteers, repaglinide had no effect on the pharmacokinetics of metformin.
Following single-dose administration of glipizide (10 mg) and repaglinide (0.5 mg) to healthy volunteers, repaglinide had no effect on the pharmacokinetics of glipizide.