PMID- 27473285
OWN - NLM
STAT- MEDLINE
DCOM- 20170328
LR  - 20221207
IS  - 1472-8206 (Electronic)
IS  - 0767-3981 (Linking)
VI  - 30
IP  - 6
DP  - 2016 Dec
TI  - Pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in healthy 
      Japanese, Chinese, and white subjects.
PG  - 625-633
LID - 10.1111/fcp.12227 [doi]
AB  - 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 [AUC(0-infinity) ] = 166.3, 165.9, and 
      185.5 h mug/mL, respectively, and 157.7, 158.5, and 181.2 h mug/mL, respectively; 
      tazobactam AUC(0-infinity) = 48.5, 43.2, and 50.1 h mug/mL, respectively, and 47.3, 43.7, 
      and 50.0 h mug/mL, respectively. The 90% CIs of their ratio estimates were within 
      the range 0.80 to 1.25 with the exception of AUC(0-infinity) 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.
CI  - (c) 2016 Societe Francaise de Pharmacologie et de Therapeutique.
FAU - Aiudi, Anthony
AU  - Aiudi A
AD  - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
FAU - Miller, Benjamin
AU  - Miller B
AD  - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
FAU - Krishna, Gopal
AU  - Krishna G
AD  - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
FAU - Adedoyin, Adedayo
AU  - Adedoyin A
AD  - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
FAU - Xiao, Alan
AU  - Xiao A
AD  - Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ, 07033, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
DEP - 20160825
PL  - England
TA  - Fundam Clin Pharmacol
JT  - Fundamental & clinical pharmacology
JID - 8710411
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cephalosporins)
RN  - 37A4IES95Q (ceftolozane)
RN  - 87-53-6 (Penicillanic Acid)
RN  - SE10G96M8W (Tazobactam)
SB  - IM
MH  - Adult
MH  - Anti-Bacterial Agents/adverse effects/pharmacokinetics
MH  - Area Under Curve
MH  - Asian People
MH  - Cephalosporins/*adverse effects/*pharmacokinetics
MH  - Drug Tolerance/*physiology
MH  - Female
MH  - Humans
MH  - Male
MH  - Penicillanic Acid/adverse effects/*analogs & derivatives/pharmacokinetics
MH  - Prospective Studies
MH  - Tazobactam
MH  - White People
OTO - NOTNLM
OT  - clinical pharmacology
OT  - infectious disease
OT  - pharmacokinetics
OT  - pharmacokinetics and drug metabolism
EDAT- 2016/07/31 06:00
MHDA- 2017/03/30 06:00
CRDT- 2016/07/31 06:00
PHST- 2016/04/12 00:00 [received]
PHST- 2016/07/25 00:00 [revised]
PHST- 2016/07/27 00:00 [accepted]
PHST- 2016/07/31 06:00 [pubmed]
PHST- 2017/03/30 06:00 [medline]
PHST- 2016/07/31 06:00 [entrez]
AID - 10.1111/fcp.12227 [doi]
PST - ppublish
SO  - Fundam Clin Pharmacol. 2016 Dec;30(6):625-633. doi: 10.1111/fcp.12227. Epub 2016 
      Aug 25.