Population pharmacokinetics of free flucloxacillin in patients treated with oral flucloxacillin plus probenecid.
Abstract
Oral flucloxacillin may be coadministered with probenecid to reduce flucloxacillin clearance and increase attainment of pharmacokinetic-pharmacodynamic (PK/PD) targets. The aims of this study were to develop a population PK model of free flucloxacillin when administered orally with probenecid, and to identify optimal dosing regimens for this combination. We performed a prospective observational study of adults (45 participants) treated with oral flucloxacillin 1000 mg and probenecid 500 mg 8-hourly for proven or probable staphylococcal infections. Steady-state mid-dose-interval flucloxacillin measurements (45 concentrations) were combined with existing data from a crossover study of healthy participants receiving flucloxacillin with and without probenecid (11 participants, 363 concentrations). We developed a population pharmacokinetic model of free flucloxacillin concentrations within Monolix, and used Monte Carlo simulation to explore optimal dosing regimens to attain PK/PD targets proposed in the literature (free drug time above minimum inhibitory concentration). Flucloxacillin disposition was best described by a 1-compartment model with a lag time and first-order absorption. Free flucloxacillin clearance depended on probenec...Continue Reading
References
Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model
Flucloxacillin, a new isoxazolyl penicillin, compared with oxacillin, cloxacillin, and dicloxacillin
Enhanced Method for Diagnosing Pharmacometric Models: Random Sampling from Conditional Distributions
Related Concepts
Related Feeds
CRISPR & Staphylococcus
CRISPR-Cas system enables the editing of genes to create or correct mutations. Staphylococci are associated with life-threatening infections in hospitals, as well as the community. Here is the latest research on how CRISPR-Cas system can be used for treatment of Staphylococcal infections.