PMID- 15215111
OWN - NLM
STAT- MEDLINE
DCOM- 20040907
LR  - 20240314
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 48
IP  - 7
DP  - 2004 Jul
TI  - Multiple-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin 
      (BAL5788) in healthy volunteers.
PG  - 2576-80
AB  - BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum 
      cephalosporin with potent bactericidal activity against methicillin-resistant 
      Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. 
      Safety and pharmacokinetic data from a multiple-dose study with 16 healthy male 
      volunteers are reported. Subjects were randomized to receive BAL5788 at 500 or 
      750 mg (as BAL9141 equivalents; n = 6 subjects per dose) or placebo (n = 2 
      subjects per dose). The doses were given as 200-ml infusions over 30 min once 
      daily on days 1 and 8 and twice daily on days 2 to 7. BAL5788 was well tolerated, 
      with no severe or serious adverse events (AEs) or dosing-related changes in 
      laboratory parameters, electrocardiographic findings, or vital signs. Drug 
      accumulation in plasma was negligible during the dosing period. The results of 
      pharmacokinetic analyses agreed well with data reported from a previous 
      single-ascending-dose study. The elimination half-life of BAL9141 was about 3 h. 
      The volume of distribution at steady state was equal to the volume of the adult 
      extracellular water compartment. BAL9141 was predominantly eliminated in urine, 
      and renal clearance of the free drug corresponded to the normal glomerular 
      filtration rate in adults. After multiple infusions of 750 mg, the mean 
      concentrations of BAL9141 in plasma exceeded the MIC at which 100% of MRSA 
      isolates are inhibited (4 microg/ml) for approximately 7 to 9 h, corresponding to 
      58 to 75% of a 12-h dosing interval.
FAU - Schmitt-Hoffmann, Anne
AU  - Schmitt-Hoffmann A
AD  - Basilea Pharmaceutica Ltd., P.O. Box 3255, Basel 4002, Switzerland. 
      schmita@basileapharma.com
FAU - Nyman, Lars
AU  - Nyman L
FAU - Roos, Brigitte
AU  - Roos B
FAU - Schleimer, Michael
AU  - Schleimer M
FAU - Sauer, Jill
AU  - Sauer J
FAU - Nashed, Norman
AU  - Nashed N
FAU - Brown, Thomas
AU  - Brown T
FAU - Man, Anthony
AU  - Man A
FAU - Weidekamm, Erhard
AU  - Weidekamm E
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Cephalosporins)
RN  - 5T97333YZK (ceftobiprole)
SB  - IM
MH  - Adult
MH  - Area Under Curve
MH  - Cephalosporins/administration & dosage/*adverse effects/*pharmacokinetics
MH  - Chromatography, Liquid
MH  - Double-Blind Method
MH  - Half-Life
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Mass Spectrometry
MH  - Molecular Weight
PMC - PMC434166
EDAT- 2004/06/25 05:00
MHDA- 2004/09/08 05:00
PMCR- 2004/07/01
CRDT- 2004/06/25 05:00
PHST- 2004/06/25 05:00 [pubmed]
PHST- 2004/09/08 05:00 [medline]
PHST- 2004/06/25 05:00 [entrez]
PHST- 2004/07/01 00:00 [pmc-release]
AID - 48/7/2576 [pii]
AID - 0385-03 [pii]
AID - 10.1128/AAC.48.7.2576-2580.2004 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2004 Jul;48(7):2576-80. doi: 
      10.1128/AAC.48.7.2576-2580.2004.