Safety, Tolerability, And Pharmacokinetics Of 3 G Of Ceftolozane/Tazobactam In Healthy Adults: A Randomized, Placebo‐Controlled, Multiple‐Dose Study
Published 2018 · Medicine
Ceftolozane/tazobactam is an antibacterial approved at 1.5 g (1g/0.5 g) every 8 hours (q8h); higher doses may provide additional benefits in difficult‐to‐treat infections. We conducted a phase I trial in healthy adults evaluating safety, tolerability, and pharmacokinetics of 3 g (2 g/1 g) ceftolozane/tazobactam administered q8h for 10 days. Sixteen participants were randomized (2:1:1) to 3 g ceftolozane/tazobactam, 1.5 g ceftolozane/tazobactam, or placebo. Participants underwent regular safety and plasma drug level assessments, with a follow‐up safety visit 7 days after completion. No adverse events (AEs) were reported with placebo; 75% of participants in the 1.5‐g and 50% in the 3‐g arm experienced AEs. AE types were similar between the ceftolozane/tazobactam groups; all AEs were mild. No participants experienced clinically meaningful laboratory assessment or electrocardiogram abnormalities. Both ceftolozane and tazobactam exhibited dose‐proportional pharmacokinetics without accumulation and without substantial differences in clearance and volume of distribution between groups. In the 3‐g group, mean ceftolozane parameters were: peak concentration 104 μg/mL (day 1), 112 μg/mL (day 10); half‐life 3 hours (day 10); area under the concentration‐time curve (AUC(0‐t)) 272 μg·h/mL (day 1), 300μg·h/mL (day 10). Mean tazobactam parameters were: peak concentration 28 μg/mL (day 1), 26 μg/mL (day 10); half‐life 1 hour (day 10); AUC(0‐t) 47μg·h/mL (day 1), 41μg·h/mL (day 10). Administration of 3 g ceftolozane/tazobactam q8h for 10 days was safe and well tolerated in healthy volunteers.