PMID- 12654665
OWN - NLM
STAT- MEDLINE
DCOM- 20030908
LR  - 20210526
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 47
IP  - 4
DP  - 2003 Apr
TI  - Daptomycin pharmacokinetics and safety following administration of escalating 
      doses once daily to healthy subjects.
PG  - 1318-23
AB  - The purpose of this paper is to establish the pharmacokinetics and safety of 
      escalating, once-daily doses of daptomycin, a novel lipopeptide antibiotic active 
      against gram-positive pathogens, including those resistant to methicillin and 
      vancomycin. This phase 1, multiple-dose, double-blind study involved 24 healthy 
      subjects in three dose cohorts (4, 6, and 8 mg/kg of body weight) who were 
      randomized to receive daptomycin or the control at a 3:1 ratio and administered 
      the study medication by a 30-min intravenous infusion every 24 h for 7 to 14 
      days. Daptomycin pharmacokinetics was assessed by blood and urine sampling. 
      Safety and tolerability were evaluated by monitoring adverse events (AEs) and 
      laboratory parameters. Daptomycin pharmacokinetics was linear through 6 mg/kg, 
      with a slight ( approximately 20%) nonlinearity in the area under the curve and 
      trough concentration at the highest dose studied (8 mg/kg). The pharmacokinetic 
      parameters measured on the median day of the study period, (day 7) were half-life 
      ( approximately 9 h), volume of distribution ( approximately 0.1 liters/kg), 
      systemic clearance ( approximately 8.2 ml/h/kg), and percentage of the drug 
      excreted intact in urine from 0 to 24 h ( approximately 54%). Daptomycin protein 
      binding (mean amount bound, 91.7%) was independent of the drug concentration. No 
      gender effect was observed. All subjects who received daptomycin completed the 
      study. The frequencies and distributions of treatment-emergent AEs were similar 
      for the subjects who received daptomycin and the control subjects. There were no 
      serious AEs and no pattern of dose-related events. The pharmacokinetics of 
      once-daily administration of daptomycin was linear through 6 mg/kg. For all three 
      doses, plasma daptomycin concentrations were consistent and predictable 
      throughout the dosing interval. Daptomycin was well tolerated when it was 
      administered once daily at a dose as high as 8 mg/kg for 14 days.
FAU - Dvorchik, Barry H
AU  - Dvorchik BH
AD  - Cubist Pharmaceuticals, Inc., Lexington, Massachusetts 02421, USA. 
      bdvorchik@cubist.com
FAU - Brazier, David
AU  - Brazier D
FAU - DeBruin, Michael F
AU  - DeBruin MF
FAU - Arbeit, Robert D
AU  - Arbeit RD
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Anti-Bacterial Agents)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - NWQ5N31VKK (Daptomycin)
SB  - IM
MH  - Adult
MH  - Anti-Bacterial Agents/*pharmacokinetics
MH  - Creatine Kinase/blood
MH  - Daptomycin/adverse effects/*pharmacokinetics
MH  - Dose-Response Relationship, Drug
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Male
PMC - PMC152488
EDAT- 2003/03/26 05:00
MHDA- 2003/09/10 05:00
PMCR- 2003/04/01
CRDT- 2003/03/26 05:00
PHST- 2003/03/26 05:00 [pubmed]
PHST- 2003/09/10 05:00 [medline]
PHST- 2003/03/26 05:00 [entrez]
PHST- 2003/04/01 00:00 [pmc-release]
AID - 0423 [pii]
AID - 10.1128/AAC.47.4.1318-1323.2003 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2003 Apr;47(4):1318-23. doi: 
      10.1128/AAC.47.4.1318-1323.2003.