Pharmacokinetics of repaglinide in subjects with renal impairment

Objective: To evaluate the effect of renal impairment and renal failure on the pharmacokinetics and safety of repaglinide. Methods: We conducted a phase I, multicenter, parallel-group, pharmacokinet ic comparison trial with single and multiple doses of repaglinide in subjec ts with various degrees of renal impairment. Subjects with normal renal fun ction (n = 6) and subjects with renal impairment (mild to moderate, n = 6; severe, n = 6) received treatment with 2 mg repaglinide for 7 days. Subject s in the hemodialysis group (n = 6) received two single doses of 2 mg repag linide separated by a 7- to 14-day washout period. All subjects had repagli nide serum pharmacokinetic profiles measured for the first and last doses a dministered. Serum steady-state levels, urine levels, and dialysate levels were also measured. Results: Pharmacokinetic parameters did not show significant changes after single or multiple doses of repaglinide, although the elimination rate cons tant in the group with severe renal impairment decreased after 1 week of tr eatment. Subjects with severe impairment had significantly higher area unde r the curve values after single and multiple doses of repaglinide than subj ects with normal renal function. No significant differences in values for m aximum serum concentration or time to reach maximum concentration were dete cted between subjects with renal impairment and those with normal renal fun ction. Hemodialysis did not significantly affect repaglinide clearance. Conclusions: Repaglinide was safe and well tolerated in subjects with varyi ng degrees of renal impairment. Although adjustment of starting doses of re paglinide is not necessary for renal impairment or renal failure, severe im pairment may require more care when upward adjustments of dosage are made.