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Stochastic process pharmacodynamics: dose timing in neonatal gentamicin therapy as an example
Tomas Radivoyevitch1, Nopphon Siranart, Lynn Hlatky
1Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.
The AAPS Journal
|February 10, 2015
Summary
A new stochastic approach to pharmacodynamics (PD) suggests larger initial antibiotic doses may improve bacterial eradication. This "hit hard early" strategy, particularly for low colony forming units (CFU), could enhance treatment effectiveness in neonates.
Area of Science:
- Pharmacokinetics/Pharmacodynamics (PK/PD)
- Stochastic Process Theory
- Infectious Disease Modeling
Background:
- Population PK/PD models estimate inter-individual variability (IIV) using statistical distributions.
- Standard deterministic models track average colony forming unit (CFU) counts.
- Tumor treatment planning integrates both deterministic and probabilistic approaches.
Purpose of the Study:
- To explore a probabilistic approach to IIV using stochastic process theory for CFU eradication.
- To contrast stochastic process PD models with standard deterministic PD models.
- To analyze neonatal intravenous gentamicin dosing regimens against Escherichia coli.
Main Methods:
- Applied stochastic process theory to model CFU eradication.
- Compared probabilistic PD models with deterministic models.
- Analyzed neonatal gentamicin dosing regimens, neglecting immune responses.
Main Results:
- Stochastic calculations indicate the first dose is critical for CFU eradication.
- A single 6 mg/kg gentamicin dose showed higher eradication probability than four daily 4 mg/kg doses.
- Stochastic models offer different insights and suggest alternative dosing regimens.
Conclusions:
- Neonatal gentamicin regimens with larger initial doses warrant investigation.
- Models predicting average CFU below 100 should incorporate stochastic effects for improved accuracy.
- Stochastic models often favor "hit hard early" strategies for better treatment outcomes.
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