Document Detail


Development and evaluation of a Bayesian pharmacokinetic estimator and optimal, sparse sampling strategies for ceftazidime.
MedLine Citation:
PMID:  8843294     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Data were gathered during an activity-controlled trial in which seriously ill, elderly patients were randomized to receive intravenous ceftazidime or ciprofloxacin and for which adaptive feedback control of drug concentrations in plasma and activity profiles was prospectively performed. The adaptive feedback control algorithm for ceftazidime used an initial population model, a maximum a posteriori (MAP)-Bayesian pharmacokinetic parameter value estimator, and an optimal, sparse sampling strategy for ceftazidime that had been derived from data in the literature obtained from volunteers. Iterative two-stage population pharmacokinetic analysis was performed to develop an unbiased MAP-Bayesian estimator and updated optimal, sparse sampling strategies. The final median values of the population parameters were follows: the volume of distribution of the central compartment was equal to 0.249 liter/kg, the volume of distribution of the peripheral compartment was equal to 0.173 liter/kg, the distributional clearance between the central and peripheral compartments was equal to 0.2251 liter/h/kg, the slope of the total clearance (CL) versus the creatinine clearance (CLCR) was equal to 0.000736 liter/h/kg of CL/1 ml/min/1.73 m2 of CLCR, and nonrenal clearance was equal to + 0.00527 liter/h/kg. Optimal sampling times were dependent on CLCR; for CLCR of > or = 30 ml/min/1.73 m2, the optimal sampling times were 0.583, 3.0, 7.0, and 16.0 h and, for CLCR of < 30 ml/min/1.73 m2, optimal sampling times were 0.583, 4.15, 11.5, and 24.0 h. The study demonstrates that because pharmacokinetic information from volunteers may often not be reflective of specialty populations such as critically ill elderly individuals, iterative two-stage population pharmacokinetic analysis, MAP-Bayesian parameter estimation, and optimal, sparse sampling strategy can be important tools in characterizing their pharmacokinetics.
Authors:
A D Kashuba; C H Ballow; A Forrest
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  40     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  1996 Aug 
Date Detail:
Created Date:  1997-01-16     Completed Date:  1997-01-16     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1860-5     Citation Subset:  IM    
Affiliation:
Center for Clinical Pharmacy Research, School of Pharmacy, State University of New York at Buffalo 14260, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Area Under Curve
Bayes Theorem
Ceftazidime / administration & dosage,  blood,  pharmacokinetics*
Cephalosporins / administration & dosage,  blood,  pharmacokinetics*
Drug Administration Schedule
Drug Therapy, Combination / administration & dosage,  pharmacokinetics
Female
Humans
Male
Middle Aged
Models, Statistical
Reference Values
Sampling Studies
Tobramycin / administration & dosage
Chemical
Reg. No./Substance:
0/Cephalosporins; 32986-56-4/Tobramycin; 78439-06-2/Ceftazidime
Comments/Corrections

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