PMID- 16423490
OWN - NLM
STAT- MEDLINE
DCOM- 20060807
LR  - 20181201
IS  - 0732-8893 (Print)
IS  - 0732-8893 (Linking)
VI  - 54
IP  - 3
DP  - 2006 Mar
TI  - Pharmacodynamic profiling of cefepime in plasma and cerebrospinal fluid of 
      hospitalized patients with external ventriculostomies.
PG  - 223-30
AB  - Population pharmacokinetic (PK) modeling and Monte Carlo simulation (MCS) were 
      used to describe the pharmacodynamic profile of cefepime in the both plasma and 
      cerebrospinal fluid (CSF). Plasma and CSF cefepime data were obtained from a PK 
      study of 7 hospitalized patients with external ventricular drains. 
      Concentration-time profiles in plasma and CSF were modeled using a 3-compartment 
      model with zero-order infusion and first-order elimination and transfer. 
      Estimates of the PK parameters were identified in the Big Non Parametric Adaptive 
      Grid with adaptive gamma (BigNPAG) program of Leary, Jelliffe, Schumitzky, and 
      Van Guilder. MCS (10,000 subjects) was performed to estimate the probability of 
      attaining the targets of free plasma concentration (20% protein binding) and 
      total drug CSF concentration of 50-100% T>minimal inhibitory concentration (MIC) 
      for MICs 0.06-8 mg/L for cefepime 2 g, iv, every 8 h (0.5-h infusion); cefepime 2 
      g, iv, every 12 h (0.5-h infusion); and cefepime 2 g (0.5-h infusion) once and 
      250 mg/h continuous infusion. After the Bayesian step, the observed-predicted 
      regression and r(2) for plasma and CNS were as follows: plasma, observed=0.984 x 
      predicted+2.570, r(2)=0.944; CSF, observed=0.785 x predicted+0.868, r(2)=0.821. 
      The median penetration of cefepime as measured by AUC(CSF)/AUC(plasma) was 7.8%. 
      In the MCS, the target attainment rates in plasma for 60-70% fT>MIC were high at 
      each MIC value between 0.03 and 8 microg/mL for each regimen examined. In CSF, 
      none of the regimens achieved 50-100% T>MIC for>80% of patients for MICs>0.5 
      mg/L.
FAU - Lodise, Thomas P Jr
AU  - Lodise TP Jr
AD  - Department of Pharmacy Practice, Albany College of Pharmacy, Albany, NY 12208, 
      USA. lodiset@acp.edu
FAU - Rhoney, Denise H
AU  - Rhoney DH
FAU - Tam, Vincent H
AU  - Tam VH
FAU - McKinnon, Peggy S
AU  - McKinnon PS
FAU - Drusano, George L
AU  - Drusano GL
LA  - eng
PT  - Journal Article
DEP - 20060119
PL  - United States
TA  - Diagn Microbiol Infect Dis
JT  - Diagnostic microbiology and infectious disease
JID - 8305899
RN  - 0 (Cephalosporins)
RN  - 807PW4VQE3 (Cefepime)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cefepime
MH  - Cephalosporins/*blood/*cerebrospinal fluid/pharmacokinetics
MH  - Female
MH  - Humans
MH  - Infusions, Intravenous
MH  - Injections, Intravenous
MH  - Male
MH  - Microbial Sensitivity Tests
MH  - Middle Aged
MH  - Models, Biological
MH  - Monte Carlo Method
MH  - Time Factors
MH  - *Ventriculostomy
EDAT- 2006/01/21 09:00
MHDA- 2006/08/08 09:00
CRDT- 2006/01/21 09:00
PHST- 2005/08/16 00:00 [received]
PHST- 2005/09/22 00:00 [accepted]
PHST- 2006/01/21 09:00 [pubmed]
PHST- 2006/08/08 09:00 [medline]
PHST- 2006/01/21 09:00 [entrez]
AID - S0732-8893(05)00237-3 [pii]
AID - 10.1016/j.diagmicrobio.2005.09.007 [doi]
PST - ppublish
SO  - Diagn Microbiol Infect Dis. 2006 Mar;54(3):223-30. doi: 
      10.1016/j.diagmicrobio.2005.09.007. Epub 2006 Jan 19.