Garenoxacin pharmacokinetics in subjects with renal impairment

Abstract

Based on the broad therapeutic index of garenoxacin, the effects of renal impairment on garenoxacin exposure are not considered clinically significant. There was a modest increase in AUC in subjects with severe renal impairment and the magnitude of the changes was not considered clinically relevant.

Optimal dose finding of garenoxacin based on population pharmacokinetics/pharmacodynamics and Monte Carlo simulation

“…2). A standard PK analysis by Krishna et al [35] reported similar results in that the the AUC in their patients with renal impairment not requiring dialysis (CL CR  < 30 ml/min) was 51% higher than that in normal subjects. The necessity of dose adjustment for special populations is suggested by Fig.…”

Pharmacokinetics of garenoxacin in elderly patients with respiratory tract infections

“…Kobayashi et al [11] reported that C max and AUC values of elderly patients (age ≥65 years) were 1.1-1.2 times higher than those of younger patients (age <65 years) and that AUC values of patients with a body weight of <40 kg and ≥40 kg were 145 g h/mL and 120 g h/mL, respectively. C max and AUC values of subjects with severe renal impairment were increased by 51% and lowered by 20%, respectively, and the terminal half-life was prolonged in subjects with severe renal impairment compared with healthy controls [9]. A GRNX dose of 400 mg is recommended, except for patients with a body weight of <40 kg and CL Cr < 30 mL/min.…”

“…GRNX is eliminated by renal excretion and hepatic metabolism, with ca. 40-50% of the dose excreted in the urine unchanged [7][8][9]. A GRNX dosage of 400 mg once daily was determined appropriate for clinical use [7].…”

Garenoxacin pharmacokinetics in patients undergoing maintenance hemodialysis

“…We were unable to calculate the T 1/2 of GRNX in the current study because the plasma concentration remained high 24 hours after administration in some cases; however, the calculated T 1/2 for the remaining patients was similar to that reported by Yamagishi et al for subjects with severe renal impairment (13.9 ± 2.2 hours after a 200 mg dose, and 13.7 ± 1.9 hours after 400 mg) . Krishna et al reported a T 1/2 in similar subjects at 32.7 ± 5 hours after a 600 mg dose . The T 1/2 for 600 mg GRNX administered once daily was prolonged in patients with severe renal impairment, regardless of whether the drug was administered 3 hours before or immediately after hemodialysis .…”

“…However, the equivalent values in patients undergoing MH in the current study were 3.0 ± 1.12 µg/mL and 40.7 ± 16.7 µg·h/mL, respectively, indicating a reduction in C max of 40%, while the AUC 0–24 values remained similar. Krishna et al reported a C max of 9.2 µg/mL and an AUC 0–24 of 156.5 µg·h/mL in MH patients receiving 600 mg GRNX once daily, while Yamagishi et al reported that MH patients receiving 200 and 400 mg GRNX once daily had C max values of 2.9 ± 0.6 and 6.0 ± 1.0 µg/mL, and AUC 0–24 values of 62.3 ± 11.9 and 128.0 ± 12.5 µg h/mL, respectively . C max and AUC 0–24 thus appear to increase in a dose‐dependent manner.…”