ABSTRACT:
HRS-8427, a development-stage siderophore cephalosporin antibiotic, is being investigated for the treatment of aerobic Gram-negative bacterial infections, encompassing urinary tract infections and pulmonary infections. Participants with these indications frequently exhibit concomitant renal impairment (RI). Data from clinical studies suggest that ~60% to ~70% of unchanged HRS-8427 is excreted renally. A phase 1, multicenter, open-label study evaluated the effects of RI on the pharmacokinetics and safety of HRS-8427. In sub-study 1, 21 participants with mild to severe RI who were not on dialysis and six participants with normal renal function received single doses of 1,000 mg HRS-8427. In sub-study 2, six participants with end-stage renal disease (ESRD) requiring hemodialysis (HD) received single doses of the 1,000 mg HRS-8427 under dialysis and non-dialysis conditions, respectively. Plasma HRS-8427 area under the concentration-time curve from zero to infinity (AUC
0–∞
) was ~1.2-fold, ~1.4-fold, 2.0-fold, and ~2.0-fold higher, respectively, in participants with mild, moderate, severe RI, and ESRD (without HD) relative to healthy controls. In dialysis-dependent subjects, the systemic exposure of HRS-8427 when dosed before HD was equivalent to 50.6% of that when dosed after HD. Adverse events (AEs) were mostly mild, and RI did not appear to be associated with an increased risk of AEs.
CLINICAL TRIALS:
This study is registered with
http://www.chinadrugtrials.org.cn/
as
CTR20230658
.