Pharmacokinetic/pharmacodynamic evaluation of tigecycline dosing in a hollow fiber infection model against clinical bla-KPC producing Klebsiella Pneumoniae isolates.

The FDA announced a boxed warning for tigecycline due to progression of infections caused by Gram-negative bacteria and increased risk of mortality during treatment. Plasma exposure of tigecycline might not prevent bacteraemia in these cases from the focuses. Hence, we evaluated intensified dosing regimens and breakpoints that might suppress bloodstream infections, caused by progression of infection by e.

Tigecycline Dosing Strategies in Critically Ill Liver-Impaired Patients.

This study investigated tigecycline exposure in critically ill patients from a population pharmacokinetic perspective to support rational dosing in intensive care unit (ICU) patients with acute and chronic liver impairment. A clinical dataset of 39 patients served as the basis for the development of a population pharmacokinetic model. The typical tigecycline clearance was strongly reduced (8.

Evaluation of the Robustness of Therapeutic Drug Monitoring Coupled with Bayesian Forecasting of Busulfan with Regard to Inaccurate Documentation.

Background: Inaccurate documentation of sampling and infusion times is a potential source of error in personalizing busulfan doses using therapeutic drug monitoring (TDM). Planned times rather than the actual times for sampling and infusion time are often documented. Therefore, this study aimed to evaluate the robustness of a limited sampling TDM of busulfan with regard to inaccurate documentation.

Stability studies with tigecycline in bacterial growth medium and impact of stabilizing agents.

Purpose: This study aimed to examine the degradation of tigecycline in Mueller Hinton broth (ca-MHB), as knowledge about bacterial susceptibility is key for therapeutic decisions.

Methods: Antioxidative stabilizers were evaluated on tigecycline stability in a quantitative chromatography assay and tigecycline induced kill against Staphylococcus aureus (ATCC29213) was determined in time kill studies.

Results: Ascorbic acid caused rapid degradation of tigecycline and resulted in loss of antibacterial activity.

An Integrated Dialysis Pharmacometric (IDP) Model to Evaluate the Pharmacokinetics in Patients Undergoing Renal Replacement Therapy.

Purpose: Clearance via renal replacement therapy (RRT) can significantly alter the pharmacokinetic profile of drugs. The aim of this study was (i) to improve the use of clinical trial data and (ii) to provide a model that allows quantification of all aspects of drug elimination via RRT including adsorption to dialysis membranes and/or degradation of the drug in the dialysate.

Methods: An integrated dialysis pharmacometric (IDP) model was developed to simultaneously incorporate all available RRT information.

Assessing parameter uncertainty in small-n pharmacometric analyses: value of the log-likelihood profiling-based sampling importance resampling (LLP-SIR) technique.

Assessing parameter uncertainty is a crucial step in pharmacometric workflows. Small datasets with ten or fewer subjects appear regularly in drug development and therapeutic use, but it is unclear which method to assess parameter uncertainty is preferable in such situations. The aim of this study was to (i) systematically evaluate the performance of standard error (SE), bootstrap (BS), log-likelihood profiling (LLP), Bayesian approaches (BAY) and sampling importance resampling (SIR) to assess parameter uncertainty in small datasets and (ii) to evaluate methods to provide proposal distributions for the SIR.

Impact of Inaccurate Documentation of Sampling and Infusion Time in Model-Informed Precision Dosing.

Background: Routine clinical TDM data is often used to develop population pharmacokinetic (PK) models, which are applied in turn for model-informed precision dosing. The impact of uncertainty in documented sampling and infusion times in population PK modeling and model-informed precision dosing have not yet been systematically evaluated. The aim of this study was to investigate uncertain documentation of (i) sampling times and (ii) infusion rate exemplified with two anti-infectives.

Pharmacokinetics of trimethoprim/sulfametrole in critically ill patients on continuous renal replacement therapy.

Objectives: We investigated the effect of continuous renal replacement therapy (CRRT) on the pharmacokinetics of trimethoprim and sulfametrole.

Patients And Methods: We enrolled critically ill adults undergoing CRRT and critically ill adults with normal or slightly impaired renal function (plasma creatinine concentration <1.5 mg/dL, control group).