Pharmacokinetics, Tolerability, and Safety of Murepavadin, a Novel Antipseudomonal Antibiotic, in Subjects with Mild, Moderate, or Severe Renal Function Impairment
Abstract
This open-label, nonrandomized, single-dose, phase 1 study evaluated the pharmacokinetics and safety of murepavadin, a novel peptide antibiotic for the treatment of serious Pseudomonas aeruginosa infections. The study was conducted in 32 subjects of either sex in 4 groups (up to 8 per group) with mild (group 1), moderate (group 2), and severe (group 3) renal function impairment or with normal renal function (group 4). The degree of renal impairment of the subjects was classified at screening according to the estimated creatinine clearance (CLCr) according to the Cockcroft-Gault equation. All subjects received a single 2.2-mg/kg of body weight intravenous infusion of murepavadin administered over 3 h. Exposure to murepavadin in plasma increased in subjects with renal function impairment, with the area under the plasma concentration-time curve from zero to infinity (AUC0-∞) increasing about 2.0- to 2.5-fold for subjects with renal function impairment compared to subjects with normal renal function, whereas the increases in maximum observed plasma concentration (Cmax) were about 1.5-fold for subjects with renal function impairment compared to subjects with normal renal function. The total clearance (CL) of murepavadin was lower in all groups of subjects with renal function impairment, with group means ranging from 2.4 liters/h to 3.8 liters/h, compared to 7.0 liters/h in subjects with normal renal function. Accordingly, the terminal elimination half-life (t1/2) prolonged up to…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 32 participants or records.
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