PMID- 29517862
OWN - NLM
STAT- MEDLINE
DCOM- 20190812
LR  - 20190812
IS  - 2160-7648 (Electronic)
IS  - 2160-763X (Linking)
VI  - 7
IP  - 4
DP  - 2018 May
TI  - Safety, Tolerability, and Pharmacokinetics of 3 g of Ceftolozane/Tazobactam in 
      Healthy Adults: A Randomized, Placebo-Controlled, Multiple-Dose Study.
PG  - 382-391
LID - 10.1002/cpdd.429 [doi]
AB  - 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 mug/mL (day 1), 
      112 mug/mL (day 10); half-life 3 hours (day 10); area under the concentration-time 
      curve (AUC((0-t)) ) 272 mug.h/mL (day 1), 300mug.h/mL (day 10). Mean tazobactam 
      parameters were: peak concentration 28 mug/mL (day 1), 26 mug/mL (day 10); 
      half-life 1 hour (day 10); AUC((0-t)) 47mug.h/mL (day 1), 41mug.h/mL (day 10). 
      Administration of 3 g ceftolozane/tazobactam q8h for 10 days was safe and well 
      tolerated in healthy volunteers.
CI  - (c) 2018, The American College of Clinical Pharmacology.
FAU - Yu, Brian
AU  - Yu B
AD  - Merck & Co, Inc, Kenilworth, NJ, USA.
FAU - Adedoyin, Adedayo
AU  - Adedoyin A
AD  - Merck & Co, Inc, Kenilworth, NJ, USA.
FAU - Hershberger, Ellie
AU  - Hershberger E
AD  - Merck & Co, Inc, Kenilworth, NJ, USA.
FAU - Caro, Luzelena
AU  - Caro L
AD  - Merck & Co, Inc, Kenilworth, NJ, USA.
FAU - Xiao, Alan
AU  - Xiao A
AD  - Merck & Co, Inc, Kenilworth, NJ, USA.
FAU - Rhee, Elizabeth G
AU  - Rhee EG
AD  - Merck & Co, Inc, Kenilworth, NJ, USA.
FAU - Huntington, Jennifer A
AU  - Huntington JA
AD  - Merck & Co, Inc, Kenilworth, NJ, USA.
LA  - eng
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20180308
PL  - United States
TA  - Clin Pharmacol Drug Dev
JT  - Clinical pharmacology in drug development
JID - 101572899
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Cephalosporins)
RN  - 0 (ceftolozane, tazobactam drug combination)
RN  - SE10G96M8W (Tazobactam)
MH  - Anti-Bacterial Agents/administration & dosage/adverse effects/*pharmacokinetics
MH  - Area Under Curve
MH  - Cephalosporins/administration & dosage/adverse effects/*pharmacokinetics
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Dosage Calculations
MH  - Female
MH  - Humans
MH  - Male
MH  - Tazobactam/administration & dosage/adverse effects/*pharmacokinetics
OTO - NOTNLM
OT  - ceftolozane
OT  - gram-negative
OT  - multidrug-resistant pathogens
OT  - pharmacokinetics
OT  - tazobactam
EDAT- 2018/03/09 06:00
MHDA- 2019/08/14 06:00
CRDT- 2018/03/09 06:00
PHST- 2017/02/14 00:00 [received]
PHST- 2017/11/26 00:00 [accepted]
PHST- 2018/03/09 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2018/03/09 06:00 [entrez]
AID - 10.1002/cpdd.429 [doi]
PST - ppublish
SO  - Clin Pharmacol Drug Dev. 2018 May;7(4):382-391. doi: 10.1002/cpdd.429. Epub 2018 
      Mar 8.