PMID- 29437614
OWN - NLM
STAT- MEDLINE
DCOM- 20190419
LR  - 20190419
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 62
IP  - 4
DP  - 2018 Apr
TI  - Phase 1 Study of the Safety, Tolerability, and Pharmacokinetics of Vaborbactam 
      and Meropenem Alone and in Combination following Single and Multiple Doses in 
      Healthy Adult Subjects.
LID - 10.1128/AAC.02228-17 [doi]
LID - e02228-17
AB  - Meropenem-vaborbactam is a fixed combination of the novel beta-lactamase inhibitor 
      vaborbactam and the carbapenem antibiotic meropenem, developed for the treatment 
      of serious infections caused by drug-resistant Gram-negative bacteria. The 
      safety, tolerability, and pharmacokinetics (PK) of vaborbactam and meropenem 
      following single and multiple ascending doses of each study drug administered 
      alone or combined were evaluated in 76 healthy adult subjects in a randomized, 
      placebo-controlled, double-blind study. Subjects were enrolled in 1 of 5 dose 
      cohorts (receiving 250 to 2,000 mg vaborbactam and/or 1,000 to 2,000 mg 
      meropenem) alone or in combination. No subjects discontinued the study due to 
      adverse events (AEs), and no serious AEs were observed. The pharmacokinetics of 
      meropenem and vaborbactam were similar when given alone or in combination; all 
      evaluated plasma PK exposure measures (peak plasma concentration, area under the 
      plasma concentration-time curve [AUC] from time zero to the last measurable 
      concentration area under the plasma concentration-time curve, and AUC from time 
      zero to infinity) were similar for the study drugs alone versus those in 
      combination, indicating no pharmacokinetic interaction between meropenem and 
      vaborbactam. Across all treatments, 47 to 64% of an administered meropenem dose 
      and 75 to 95% of vaborbactam was excreted unchanged in the urine over 48 h 
      postdose. Meropenem and vaborbactam, when given alone or in combination, have 
      similar pharmacokinetic properties, with no plasma or urine PK drug-drug 
      interactions, and are well tolerated. These findings supported further clinical 
      investigation of the combination product. (This study is registered at 
      ClinicalTrials.gov under registration no. NCT01897779.).
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Rubino, Christopher M
AU  - Rubino CM
AD  - Institute for Clinical Pharmacodynamics, Schenectady, New York, USA.
FAU - Bhavnani, Sujata M
AU  - Bhavnani SM
AD  - Institute for Clinical Pharmacodynamics, Schenectady, New York, USA.
FAU - Loutit, Jeffery S
AU  - Loutit JS
AD  - The Medicines Company, San Diego, California, USA.
FAU - Morgan, Elizabeth E
AU  - Morgan EE
AD  - The Medicines Company, San Diego, California, USA.
FAU - White, Dan
AU  - White D
AD  - The Medicines Company, San Diego, California, USA.
FAU - Dudley, Michael N
AU  - Dudley MN
AD  - The Medicines Company, San Diego, California, USA.
FAU - Griffith, David C
AU  - Griffith DC
AD  - The Medicines Company, San Diego, California, USA david.griffith@themedco.com.
LA  - eng
SI  - ClinicalTrials.gov/NCT01897779
PT  - Clinical Trial, Phase I
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20180327
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Boronic Acids)
RN  - 1C75676F8V (vaborbactam)
RN  - FV9J3JU8B1 (Meropenem)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Boronic Acids/*adverse effects/*pharmacokinetics
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Interactions
MH  - Female
MH  - Healthy Volunteers
MH  - Humans
MH  - Male
MH  - Meropenem/*adverse effects/*pharmacokinetics
MH  - Middle Aged
MH  - Young Adult
PMC - PMC5914003
OTO - NOTNLM
OT  - beta-lactamase
OT  - drug interaction
OT  - meropenem
OT  - pharmacokinetics
OT  - vaborbactam
EDAT- 2018/02/14 06:00
MHDA- 2019/04/20 06:00
PMCR- 2018/09/27
CRDT- 2018/02/14 06:00
PHST- 2017/10/27 00:00 [received]
PHST- 2018/01/25 00:00 [accepted]
PHST- 2018/02/14 06:00 [pubmed]
PHST- 2019/04/20 06:00 [medline]
PHST- 2018/02/14 06:00 [entrez]
PHST- 2018/09/27 00:00 [pmc-release]
AID - AAC.02228-17 [pii]
AID - 02228-17 [pii]
AID - 10.1128/AAC.02228-17 [doi]
PST - epublish
SO  - Antimicrob Agents Chemother. 2018 Mar 27;62(4):e02228-17. doi: 
      10.1128/AAC.02228-17. Print 2018 Apr.