Plazomicin Pharmacokinetics in Indian Complicated Urinary Tract Infections Patients: A Subgroup Analysis from a Phase...

Area of Science:

• Pharmacology and Infectious Diseases
• Clinical Pharmacokinetics
• Antimicrobial Resistance

Background:

• Multidrug-resistant Enterobacteriaceae are a significant cause of complicated urinary tract infections (cUTIs).
• Understanding drug pharmacokinetics (PK) in diverse populations is crucial for effective treatment.
• Plazomicin is an aminoglycoside antibiotic used for treating cUTIs.

Purpose of the Study:

• To compare the pharmacokinetic (PK) parameters of plazomicin between Indian and non-Indian participants.
• To evaluate plazomicin exposure in patients with complicated urinary tract infections or acute pyelonephritis.

Main Methods:

• Post hoc analysis of PK data from a Phase 2 multicenter, double-blind, randomized study (ACHN-490-002).
• Participants (aged 18-85 years, body weight ≤100 kg) received plazomicin at 10 or 15 mg/kg.
• PK parameters, including area under the plasma time-concentration curve (AUC0-24) and maximum concentration (Cmax), were analyzed.

Main Results:

• Plazomicin at 15 mg/kg showed higher AUC0-24 and Cmax than the 10 mg/kg dose, with greater variability.
• At the 10 mg/kg dose, mean AUC0-24 was 163.0 mg•h/L for Indian participants and 185.0 mg•h/L for non-Indian participants.
• Mean Cmax was 17.2 mg•h/L for Indian and 15.7 mg•h/L for non-Indian participants, indicating comparable plazomicin exposure across groups.

Conclusions:

• Estimated mean plazomicin AUC0-24 values were comparable between Indian and non-Indian participants.
• Dose-normalized PK parameters (AUC0-24 and Cmax) were similar, suggesting comparable plazomicin exposure.
• These findings support the use of plazomicin in diverse patient populations for treating complicated urinary tract infections.