Preliminary clinical evaluation of cefmetazole dosing regimens in Japanese patients with urinary tract infections.

BACKGROUND: Cefmetazole (CMZ) is widely used in Japan to treat infections such as urinary tract infections (UTIs), intra-abdominal infections, and bloodstream infections. However, pharmacokinetic and pharmacodynamic (PK/PD) data supporting the appropriate use of CMZ in Japanese patients with UTIs remain limited. Thus, as a preliminary study, we evaluated steady-state plasma concentrations of CMZ in Japanese patients with mild to moderate UTIs. METHODS: Twenty-three patients with mild to moderate UTIs admitted to the Department of Urology at Gifu Prefectural General Medical Center from October 2022 to January 2023 were enrolled. Two patients were excluded due to inappropriate sampling timing and lack of steady-state samples, resulting in 21 patients included in the final analysis. Repeated doses of cefmetazole (CMZ, 1 g-per dose) were administered at various intervals (6, 8, 12, or 24 h) based on renal function. Steady-state plasma samples 2–3.25 h after infusion (near peak) as well as just before the next dose (near trough) were collected. Plasma concentrations of CMZ were measured using a validated high-performance liquid chromatography (HPLC) method. The relationship between plasma concentrations of CMZ and creatinine clearance (Ccr) was analyzed. RESULTS: CMZ effectively treated ESBL-E-induced UTIs in all patients (n = 5). With CMZ dosing regimens based on renal function, the mean (± SD) steady-state plasma concentrations at near-peak and near-trough were 73.8 ± 27.1 µg/mL and 14.0 ± 11.0 µg/mL, respectively. Steady-state near-peak plasma concentrations of CMZ (n = 19) were found to be negatively correlated with Ccr (R = − 0.70, p < 0.001). However, there is no correlation between Ccr and near-trough plasma concentrations of CMZ (n = 11, R = − 0.53). CONCLUSIONS: Preliminary clinical data suggest the potential appropriateness of the CMZ dosing regimen in patients with mild to moderate UTIs based on renal function, although further detailed population PK/PD analysis would be necessary.