Population pharmacokinetics of @entity3400 in the early phase of XXXX -does standard dosing result in therapeutic plasma concentrations?

@entity1 @entity8 @entity796 @entity326 @entity7120 @entity1726 @entity24523 @entity3400 @entity1011
UNASSIGNED: Antibiotic dosing in @entity326 @entity1 poses a challenge for clinicians due to the pharmacokinetic variability seen in this @entity1 population. @entity3400 / @entity7120 is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of @entity3400 (4 g) every 8 hours, during the third consecutive dosing interval, in 15 @entity1 treated empirically for @entity326 . We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the minimal inhibitory concentration (T>MIC) predicted for each @entity1 was evaluated against clinical breakpoint MIC for @entity796 (16 mg/L). Pharmacokinetic-pharmacodynamic ( @entity24523 / @entity1726 ) targets evaluated were 50% fT>4xMIC and 100% f T>MIC. A population @entity24523 model was developed using NONMEM and data was best described by a two-compartment model. Central and inter-compartmental clearances were 3.6 L/h (RSE 15.7%) and 6.58 (16.4%), and central and peripheral volumes were 7.3 L (RSE 11.8 %) and 3.9 L (RSE 9.7%), respectively. @entity3400 plasma concentrations varied considerably between @entity1 and were associated with levels of plasma @entity1011 . @entity1 with @entity8 were more likely to achieve predefined @entity24523 / @entity1726 targets compared to @entity1 with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For @entity326 @entity1 with preserved or augmented renal function, dose increment or prolonged infusion of the drug need to be considered.
