PMID- 23295928
OWN - NLM
STAT- MEDLINE
DCOM- 20130730
LR  - 20231213
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Print)
IS  - 0066-4804 (Linking)
VI  - 57
IP  - 3
DP  - 2013 Mar
TI  - Single- and multiple-dose study to determine the safety, tolerability, and 
      pharmacokinetics of ceftaroline fosamil in combination with avibactam in healthy 
      subjects.
PG  - 1496-504
LID - 10.1128/AAC.02134-12 [doi]
AB  - This study was conducted to determine the safety, tolerability, and 
      pharmacokinetics of intravenous doses of ceftaroline fosamil administered in 
      combination with the novel non-beta-lactam beta-lactamase inhibitor avibactam in 
      healthy adults. In the single-dose, open-label arm, 12 subjects received single 
      1-h intravenous infusions of ceftaroline fosamil alone (600 mg), avibactam alone 
      (600 mg), and ceftaroline fosamil in combination with avibactam (600/600 mg) 
      separated by 5-day washout periods. In the multiple-dose, placebo-controlled, 
      double-blind arm, 48 subjects received intravenous infusions of ceftaroline 
      fosamil/avibactam at 600/600 mg every 12 h (q12h), 400/400 mg q8h, 900/900 mg 
      q12h, 600/600 mg q8h, or placebo for 10 days. Ceftaroline and avibactam levels in 
      plasma and urine were measured by liquid chromatography coupled with tandem mass 
      spectrometry. No significant differences in systemic exposure of ceftaroline or 
      avibactam were observed when the drugs were administered alone versus 
      concomitantly, indicating that there was no apparent pharmacokinetic interaction 
      between ceftaroline fosamil and avibactam administered as a single dose. No 
      appreciable accumulation of either drug occurred with multiple intravenous doses 
      of ceftaroline fosamil/avibactam, and pharmacokinetic parameters for ceftaroline 
      and avibactam were similar on days 1 and 10. Infusions of ceftaroline 
      fosamil/avibactam were well tolerated at total daily doses of up to 1,800 mg of 
      each compound, and all adverse events (AEs) were mild to moderate in severity. 
      Infusion-site reactions were the most common AEs reported with multiple dosing. 
      The pharmacokinetic and safety profiles of ceftaroline fosamil/avibactam 
      demonstrate that the 2 drugs can be administered concomitantly to provide an 
      important broad-spectrum antimicrobial treatment option.
FAU - Riccobene, Todd A
AU  - Riccobene TA
AD  - Forest Research Institute, Inc., Jersey City, NJ, USA. todd.riccobene@frx.com
FAU - Su, Sheng Fang
AU  - Su SF
FAU - Rank, Douglas
AU  - Rank D
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130107
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - 0 (Azabicyclo Compounds)
RN  - 0 (Cephalosporins)
RN  - 0 (Drug Combinations)
RN  - 0 (Placebos)
RN  - 7352665165 (avibactam)
SB  - IM
MH  - Adult
MH  - Anti-Bacterial Agents/blood/*pharmacokinetics/urine
MH  - Azabicyclo Compounds/blood/*pharmacokinetics/urine
MH  - Cephalosporins/blood/*pharmacokinetics/urine
MH  - Chromatography, Liquid
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Female
MH  - Humans
MH  - Injections, Intravenous
MH  - Male
MH  - Middle Aged
MH  - Placebos
MH  - Tandem Mass Spectrometry
MH  - Ceftaroline
PMC - PMC3591900
EDAT- 2013/01/09 06:00
MHDA- 2013/07/31 06:00
PMCR- 2013/09/01
CRDT- 2013/01/09 06:00
PHST- 2013/01/09 06:00 [entrez]
PHST- 2013/01/09 06:00 [pubmed]
PHST- 2013/07/31 06:00 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - AAC.02134-12 [pii]
AID - 02134-12 [pii]
AID - 10.1128/AAC.02134-12 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2013 Mar;57(3):1496-504. doi: 10.1128/AAC.02134-12. 
      Epub 2013 Jan 7.