PMID- 21361783
OWN - NLM
STAT- MEDLINE
DCOM- 20111128
LR  - 20131121
IS  - 1941-2703 (Electronic)
IS  - 1941-2711 (Linking)
VI  - 24
IP  - 4
DP  - 2011 Aug
TI  - Pharmacokinetics and tolerability of amikacin administered as BAY41-6551 aerosol 
      in mechanically ventilated patients with gram-negative pneumonia and acute renal 
      failure.
PG  - 183-90
LID - 10.1089/jamp.2010.0860 [doi]
AB  - BACKGROUND: BAY41-6551, a drug-device combination in development for adjunctive 
      treatment of Gram-negative pneumonia in intubated and mechanically ventilated 
      patients, consists of amikacin formulated for inhalation coupled with the 
      Pulmonary Drug Delivery System (PDDS) Clinical aerosol delivery platform. Given 
      the predominantly renal clearance of aminoglycosides, understanding systemic 
      amikacin exposure and safety during administration of BAY41-6551 to patients with 
      acute renal failure (ARF) is clinically important. METHODS: Seven mechanically 
      ventilated patients with Gram-negative pneumonia and ARF receiving continuous 
      veno-venous hemodiafiltration (CVVHDF) were treated with multiple administrations 
      of BAY41-6551 400 mg amikacin twice daily using the PDDS Clinical on-ventilator 
      device [in addition to standard intravenous (i.v.) antimicrobial therapy]. CVVHDF 
      parameters were recorded and a PK analysis was performed using serum, urine, and 
      bronchoalveolar lavage fluid samples. RESULTS: Maximum serum amikacin 
      concentration [median 1.93 (range: 0.63-3.99) mg/L] and area under the 
      concentration-time curve from zero to 12 h on day 3 [median 19.32 (range 
      6.32-36.87) mg . h/L] were elevated compared with mechanically ventilated 
      patients with normal renal function; however, serum amikacin trough 
      concentrations were within accepted safety limits. The median amikacin 
      concentration in epithelial lining fluid [887 (range: 406-12,819) mg/L] was 
      similar to that reported previously in mechanically ventilated patients with 
      normal renal function. BAY41-6551 demonstrated acceptable safety and tolerability 
      with most adverse events (AEs) as expected for the patient population. One 
      serious AE of bronchospasm was attributed to the study medication; no reported 
      AEs were related to the PDDS Clinical device. CONCLUSIONS: CVVHDF appears to 
      provide adequate clearance of systemically absorbed amikacin in mechanically 
      ventilated patients with ARF, suggesting that dose adjustments for BAY41-6551 are 
      probably not necessary for this patient population. Nonetheless, the standard 
      precautionary measures for critically ill patients receiving i.v. amikacin should 
      be followed for patients with ARF who are treated with BAY41-6551.
FAU - Luyt, Charles-Edouard
AU  - Luyt CE
AD  - Service de Reanimation Medicale, Hopital Pitie-Salpetriere, Paris, France. 
      charles-edouard.luyt@psl.ap-hop-paris.fr
FAU - Eldon, Michael A
AU  - Eldon MA
FAU - Stass, Heino
AU  - Stass H
FAU - Gribben, Dennis
AU  - Gribben D
FAU - Corkery, Kevin
AU  - Corkery K
FAU - Chastre, Jean
AU  - Chastre J
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110301
PL  - United States
TA  - J Aerosol Med Pulm Drug Deliv
JT  - Journal of aerosol medicine and pulmonary drug delivery
JID - 101475057
RN  - 0 (Aerosols)
RN  - 0 (Anti-Bacterial Agents)
RN  - 84319SGC3C (Amikacin)
MH  - Acute Kidney Injury/complications
MH  - Aerosols
MH  - Aged
MH  - Amikacin/*administration & dosage/adverse effects/pharmacokinetics
MH  - Anti-Bacterial Agents/*administration & dosage/adverse effects/pharmacokinetics
MH  - Area Under Curve
MH  - Critical Illness
MH  - Drug Delivery Systems
MH  - Female
MH  - Follow-Up Studies
MH  - Gram-Negative Bacterial Infections/*drug therapy
MH  - Hemodiafiltration/methods
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Pneumonia, Bacterial/*drug therapy/microbiology
MH  - Respiration, Artificial
MH  - Tissue Distribution
EDAT- 2011/03/03 06:00
MHDA- 2011/12/13 00:00
CRDT- 2011/03/03 06:00
PHST- 2011/03/03 06:00 [entrez]
PHST- 2011/03/03 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
AID - 10.1089/jamp.2010.0860 [doi]
PST - ppublish
SO  - J Aerosol Med Pulm Drug Deliv. 2011 Aug;24(4):183-90. doi: 
      10.1089/jamp.2010.0860. Epub 2011 Mar 1.