ArticleBritish journal of clinical pharmacology2004
Quantitative justification for target concentration intervention--parameter variability and predictive performance using population pharmacokinetic models for aminoglycosides.
Article in British journal of clinical pharmacology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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56 citing papers in PubMed, 109 citations in OpenAlex.
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- The Significance of Bayesian Pharmacokinetics in Dosing for Critically Ill Patients: A Primer for Clinicians Using Vancomycin as an Example.Antibiotics (Basel, Switzerland) · 2023Review
- Cefepime Population Pharmacokinetics, Antibacterial Target Attainment, and Estimated Probability of Neurotoxicity in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2023Article
- Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients.The Journal of antimicrobial chemotherapy · 2023Article
- Consistent methods for fat-free mass, creatinine clearance, and glomerular filtration rate to describe renal function from neonates to adults.CPT: pharmacometrics & systems pharmacology · 2023Article
- Population Pharmacokinetic Model for Unbound Concentrations of Daptomycin in Patients with MRSA Including Patients Undergoing Hemodialysis.European journal of drug metabolism and pharmacokinetics · 2023Article
- Considerations for Intravenous Anesthesia Dose in Obese Children: Understanding PKPD.Journal of clinical medicine · 2023Review
- Influence of Renal Function on Phosphoramide Mustard Exposure: A Nonlinear Mixed-Effects Analysis.Journal of clinical pharmacology · 2023Article
- Clinical Pharmacokinetics of Gentamicin in Various Patient Populations and Consequences for Optimal Dosing for Gram-Negative Infections: An Updated Review.Clinical pharmacokinetics · 2022Review
- Population pharmacokinetics of clofarabine for allogeneic hematopoietic cell transplantation in paediatric patients.British journal of clinical pharmacology · 2021Article
- Target-Controlled Infusion of Cefepime in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2019Article
- A Fast Parameter Identification Framework for Personalized Pharmacokinetics.Scientific reports · 2019Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims[1] To quantify the random and predictable components of variability for aminoglycoside clearance and volume of distribution [2] To investigate models for predicting aminoglycoside clearance in patients with low serum creatinine concentrations [3] To evaluate the predictive performance of initial dosing strategies for achieving an aminoglycoside target concentration.
methodsAminoglycoside demographic, dosing and concentration data were collected from 697 adult patients (> or =20 years old) as part of standard clinical care using a target concentration intervention approach for dose individualization. It was assumed that aminoglycoside clearance had a renal and a nonrenal component, with the renal component being linearly related to predicted creatinine clearance.
resultsA two compartment pharmacokinetic model best described the aminoglycoside data. The addition of weight, age, sex and serum creatinine as covariates reduced the random component of between subject variability (BSVR) in clearance (CL) from 94% to 36% of population parameter variability (PPV). The final pharmacokinetic parameter estimates for the model with the best predictive performance were: CL, 4.7 l h(-1) 70 kg(-1); intercompartmental clearance (CLic), 1 l h(-1) 70 kg(-1); volume of central compartment (V1), 19.5 l 70 kg(-1); volume of peripheral compartment (V2) 11.2 l 70 kg(-1).
conclusionsUsing a fixed dose of aminoglycoside will achieve 35% of typical patients within 80-125% of a required dose. Covariate guided predictions increase this up to 61%. However, because we have shown that random within subject variability (WSVR) in clearance is less than safe and effective variability (SEV), target concentration intervention can potentially achieve safe and effective doses in 90% of patients.
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