PMID- 15215110
OWN - NLM
STAT- MEDLINE
DCOM- 20040907
LR  - 20240317
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 48
IP  - 7
DP  - 2004 Jul
TI  - Single-dose pharmacokinetics and safety of a novel broad-spectrum cephalosporin 
      (BAL5788) in healthy volunteers.
PG  - 2570-5
AB  - BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum 
      cephalosporin with potent bactericidal activities against methicillin-resistant 
      Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. 
      We investigated the safety and pharmacokinetics of BAL5788 in a double-blind, 
      single-ascending-dose study with 40 healthy male subjects. The subjects were 
      randomized to receive placebo (n = 2 subjects per dose) or BAL5788 (n = 6 
      subjects per dose) as a 200-ml intravenous infusion over 30 min. The BAL5788 
      doses used were 125, 250, 500, 750, and 1,000 mg (BAL9141 equivalents). All doses 
      were well tolerated, with no severe or serious adverse events (AEs). The most 
      frequent AE was taste disturbance. No electrocardiographic abnormalities and no 
      trends or clinically significant changes in laboratory parameters or vital signs 
      were observed. The maximum concentration of drug in serum and the area under the 
      concentration-time curve for BAL9141 were dose proportional over the dosing 
      range. 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, and the rate of renal clearance of free drug corresponded to 
      the normal glomerular filtration rate for adults. More than 70% of the 
      administered dose was excreted as BAL9141 in the urine, and almost no prodrug was 
      detected. After the infusion of 750 mg, the mean plasma BAL9141 concentrations 
      exceeded the MIC at which 100% of MRSA isolates are inhibited (4 microg/ml) for 
      approximately 7 h, or 58% of a 12-h dosing interval. These results indicate that 
      infusions of 750 mg twice a day should be adequate for the treatment of 
      infections caused by MRSA.
FAU - Schmitt-Hoffmann, Anne
AU  - Schmitt-Hoffmann A
AD  - Basilea Pharmaceutica Ltd., P.O. Box 3255, Basel 4002, Switzerland. 
      schmita@basileapharma.com
FAU - Roos, Brigitte
AU  - Roos B
FAU - Schleimer, Michael
AU  - Schleimer M
FAU - Sauer, Jill
AU  - Sauer J
FAU - Man, Anthony
AU  - Man A
FAU - Nashed, Norman
AU  - Nashed N
FAU - Brown, Thomas
AU  - Brown T
FAU - Perez, Antonio
AU  - Perez A
FAU - Weidekamm, Erhard
AU  - Weidekamm E
FAU - Kovacs, Peter
AU  - Kovacs P
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/*adverse effects/*pharmacokinetics
MH  - Chromatography, Liquid
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Half-Life
MH  - Humans
MH  - Infusions, Intravenous
MH  - Male
MH  - Mass Spectrometry
PMC - PMC434165
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 - 48/7/2570 [pii]
AID - 0384-03 [pii]
AID - 10.1128/AAC.48.7.2570-2575.2004 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2004 Jul;48(7):2570-5. doi: 
      10.1128/AAC.48.7.2570-2575.2004.