Population pharmacokinetic modeling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery

Staatz, Christine E., Byrne, Colette and Thomson, Alison H. (2006) Population pharmacokinetic modeling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery. British Journal of Clinical Pharmacology, 61 2: 164-176. doi:10.1111/j.1365-2125.2005.02547.x


Author Staatz, Christine E.
Byrne, Colette
Thomson, Alison H.
Title Population pharmacokinetic modeling of gentamicin and vancomycin in patients with unstable renal function following cardiothoracic surgery
Journal name British Journal of Clinical Pharmacology   Check publisher's open access policy
ISSN 0306-5251
1365-2125
Publication date 2006-01-01
Sub-type Article (original research)
DOI 10.1111/j.1365-2125.2005.02547.x
Volume 61
Issue 2
Start page 164
End page 176
Total pages 13
Place of publication United Kingdom
Publisher Blackwell
Collection year 2006
Language eng
Subject C1
320503 Clinical Pharmacology and Therapeutics
730000 - Health
Formatted abstract
Aims

To describe the population pharmacokinetics of gentamicin and vancomycin in cardiothoracic surgery patients with unstable renal function.

Methods

Data collected during routine care were analyzed using NONMEM. Linear relationships between creatinine clearance (CLCr) and drug clearance (CL) were identified, and two approaches to modelling changing CLCr were examined. The first included baseline (BCOV) and difference from baseline (DCOV) effects and the second allowed the influence of CLCr to vary between individuals. Final model predictive performance was evaluated using independent data. The data sets were then combined and parameters re-estimated.

Results

Model building was performed using data from 96 (gentamicin) and 102 (vancomycin) patients, aged 17–87 years. CLCr ranged from 9 to 172 ml min−1 and changes varied from −76 to 58 ml min−1 (gentamicin) and −86 to 93 ml min−1 (vancomycin). Inclusion of BCOV and DCOV improved the fit of the gentamicin data but had little effect on that for vancomycin. Inclusion of interindividual variability (IIV) in the influence of CLcr resulted in a poorly characterized model for gentamicin and had no effect on vancomycin modelling. No bias was seen in population compared with individual CL estimates in independent data from 39 (gentamicin) and 37 (vancomycin) patients. Mean (95% CI) differences were 4% (−3, 11%) and 2% (−2, 6%), respectively. Final estimates were: CLGent (l h−1) = 2.81 × (1 + 0.015 × (BCOVCLCr-BCOVCLCr Median) + 0.0174 × DCOVCLCr); CLVanc (l h−1) = 2.97 × (1 + 0.0205 × (CLCr-CLCr Median)). IIV in CL was 27% for both drugs.

Conclusions

A parameter describing individual changes in CLcr with time improves population pharmacokinetic modelling of gentamicin but not vancomycin in clinically unstable patients.
Keyword Pharmacology & Pharmacy
cardiothoracic surgery
gentamicin
population pharmacokinetics
vancomycin
Critically Ill Patients
Creatinine Clearance
Risk-factors
Endocarditis
Therapy
Weight
Cancer
Q-Index Code C1

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
School of Pharmacy Publications
 
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Created: Wed, 15 Aug 2007, 20:09:53 EST