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New publication: Pfizer group use Simcyp in assessment of linezolid pharmacokinetics
Date: 16 Apr 2010
A paper to be published in the Journal of Clinical Pharmacology describes a study undertaken to systematically evaluate the effect of rifampin on the pharmacokinetics of linezolid in healthy volunteers.
The investigation, by Kuan Gandelman and colleagues at Pfizer, demonstrated that coadministration with rifampin reduced the area under the plasma concentration-time curve and maximum concentration values for linezolid.
In vitro induction data using human hepatocytes, as well as physiologically-based pharmacokinetic (PBPK) modelling using the Simcyp Population-based ADME Simulator, were used to evaluate this interaction and support the clinical observations. The simulation results suggested that rifampin-inducible drug metabolising enzymes, such as CYP3A, only play a minor role in linezolid clearance.
The authors conclude that linezolid administered alone, or in combination with rifampin, was generally safe and well-tolerated in healthy subjects and the clinical significance of decreased linezolid levels due to coadministration with rifampin remains unclear.
The paper is entitled ‘Unexpected effect of rifampin on the pharmacokinetics of linezolid: in silico and in vitro approaches to explain its mechanism.’ Please see click here to link to the abstract and full text options.