Relebactam/imipenem/cilastatin is approved in the US to treat complicated urinary tract and intra-abdominal infections in patients that have limited or no alternative treatment options and HABP/VABP. Initial pharmacokinetic, safety, and tolerability studies of relebactam with and without imipenem/cilastatin included mostly Caucasian participants. This study evaluated pharmacokinetics, safety, and tolerability of relebactam/imipenem/cilastatin in 12 healthy Chinese participants after three single doses of increasing concen tration (relebactam 125, 250, or 500 mg/cilastatin 250, 500, or 1000 mg/imipenem 250, 500, or 1000 mg) and after multiple doses every 6 h of a single concentration (relebactam 250 mg/cilastatin 500 mg/imipenem 500 mg) for 14 days. After single doses, area under the concentration–time curve (AUC) extrapolated to infinity (relebactam, 15.0–70.7 h*mg/liter; imipenem, 24.1–109.8 h*mg/liter; cilastatin, 18.4–95.3 h*mg/liter) and AUC from 0–6 h (relebactam, 14.2–66.3 h*mg/liter; imipenem, 23.4–107.3 h*mg/liter; cilastatin, 18.3–94.4 h*mg/liter) increased in a dose-dependent manner; clearance (relebactam, 6.9–8.3 liters/h; imipenem, 8.6–10.4 liters/h; cilastatin, 10.5–13.6 liters/h) and half-life (relebactam, 1.4–1.6 h; imipenem, 1.0–1.2 h; cilastatin, 0.7–1.0 h) were consistent between doses. Pharmacokinetic parameters after multiple doses were similar to parameters after a single dose (geometric mean ratios of 0.8–1.0 for all three agents). Relebactam/imipen em/cilastatin was well tolerated; mild adverse events occurred during single dosing, and one participant experienced serious adverse events after multiple doses. Pharmacokinetics and safety data are comparable with data from participants of other ethnicities, supporting the use of relebactam/imipenem/cilastatin at the approved dose and schedule in Chinese patients.
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου
Σημείωση: Μόνο ένα μέλος αυτού του ιστολογίου μπορεί να αναρτήσει σχόλιο.