Pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in healthy Japanese, Chinese, and white subjects.

ABSTRACT

Ceftolozane/tazobactam, a novel antibacterial with potent activity against Gram-negative pathogens, was developed for treatment of complicated urinary tract infections, including pyelonephritis, and intra-abdominal infections. A phase 1 pharmacokinetic (PK) study of ceftolozane/tazobactam in healthy Japanese, Chinese, and white volunteers was conducted to assess the potential effect of ethnicity on PK. The PK of ceftolozane, tazobactam, and tazobactam metabolite M1 was compared after single 1.5- and 3-g intravenous doses of ceftolozane/tazobactam. Ten Japanese, nine Chinese, and ten white subjects were enrolled, and 27 completed all doses of study medication. Dose-normalized PK parameters for ceftolozane and tazobactam were similar among Japanese, Chinese, and white subjects (at 1.5-g and 3-g doses, ceftolozane area under the plasma concentration-time curve from zero to infinity [AUC0-∞ ] = 166.3, 165.9, and 185.5 h µg/mL, respectively, and 157.7, 158.5, and 181.2 h µg/mL, respectively; tazobactam AUC0-∞ = 48.5, 43.2, and 50.1 h µg/mL, respectively, and 47.3, 43.7, and 50.0 h µg/mL, respectively. The 90% CIs of their ratio estimates were within the range 0.80 to 1.25 with the exception of AUC0-∞ for ceftolozane after the 3-g dose (0.79). The cumulative amount of ceftolozane and tazobactam excreted in urine was similar among ethnic groups. For all groups, treatment-emergent adverse events (AEs) were mild; no deaths or serious AEs were reported. The PK of ceftolozane/tazobactam was approximately dose proportional (i.e. doubling the dose approximately doubles the exposure) and similar among the groups. No dosage adjustment is needed for ceftolozane/tazobactam in Japanese and Chinese patients.