Software for Dosage Individualization of Voriconazole: a Prospective Clinical Study.

Voriconazole is a first-line antifungal agent. Therapeutic drug monitoring is a standard of care. The best way to adjust dosages to achieve desired drug exposure endpoints is unclear due to nonlinear and variable pharmacokinetics.

Pharmacodynamics of the Novel Antifungal Agent F901318 for Acute Sinopulmonary Aspergillosis Caused by Aspergillus flavus.

Background: Aspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics (PD) of the lead compound F901318 is required to plan safe and effective regimens for clinical use.

Pharmacodynamics of teicoplanin against MRSA.

Objectives: The overall study aim was to identify the relevant preclinical teicoplanin pharmacokinetic (PK)/pharmacodynamic (PD) indices to predict efficacy and suppression of resistance in MRSA infection.

Methods: A hollow-fibre infection model and a neutropenic murine thigh infection model were developed. The PK/PD data generated were modelled using a non-parametric population modelling approach with Pmetrics.

Tools for the Individualized Therapy of Teicoplanin for Neonates and Children.

The aim of this study was to develop a population pharmacokinetic (PK) model for teicoplanin across childhood age ranges to be used as Bayesian prior information in the software constructed for individualized therapy. We developed a nonparametric population model fitted to PK data from neonates, infants, and older children. We then implemented this model in the BestDose multiple-model Bayesian adaptive control algorithm to show its clinical utility.

Population pharmacokinetics and dosing considerations for the use of daptomycin in adult patients with haematological malignancies.

Objectives: To assess the population pharmacokinetics (popPK) of daptomycin at the conventional dose of 6 mg/kg/day in a cohort of oncohaematological patients.

Methods: Patients underwent serial blood sampling on day 3 of therapy (before dosing and at 0, 0.5, 1, 2, 3, 5, 7, 9 and 12 h after dosing) to assess the pharmacokinetic profile of daptomycin.

The role of infection models and PK/PD modelling for optimising care of critically ill patients with severe infections.

Critically ill patients with severe infections are at high risk of suboptimal antimicrobial dosing. The pharmacokinetics (PK) and pharmacodynamics (PD) of antimicrobials in these patients differ significantly from the patient groups from whose data the conventional dosing regimens were developed. Use of such regimens often results in inadequate antimicrobial concentrations at the site of infection and is associated with poor patient outcomes.

Population Pharmacokinetics and Pharmacodynamics of Levofloxacin in Acutely Hospitalized Older Patients with Various Degrees of Renal Function.

A retrospective study was conducted in a large sample of acutely hospitalized older patients who underwent therapeutic drug monitoring during levofloxacin treatment. The aim was to assess the population pharmacokinetics (popPK) and pharmacodynamics of levofloxacin among older patients. PopPK and Monte Carlo simulation were performed to define the permissible doses in older patients according to various degrees of renal function.

Population pharmacokinetics and pharmacodynamics of teicoplanin in neonates: making better use of C-reactive protein to deliver individualized therapy.

Objectives: There is uncertainty about the optimal teicoplanin regimens for neonates. The study aim was to determine the population pharmacokinetics (PK) of teicoplanin in neonates, evaluate currently recommended regimens and explore the exposure-effect relationships.

Methods: An open-label PK study was conducted.

Pharmacodynamics of Voriconazole in Children: Further Steps along the Path to True Individualized Therapy.

Voriconazole is the agent of choice for the treatment of invasive aspergillosis in children at least 2 years of age. The galactomannan index is a routinely used diagnostic marker for invasive aspergillosis and can be useful for following the clinical response to antifungal treatment. The aim of this study was to develop a pharmacokinetic-pharmacodynamic (PK-PD) mathematical model that links the pharmacokinetics of voriconazole with the galactomannan readout in children.

Pharmacodynamics of vancomycin for CoNS infection: experimental basis for optimal use of vancomycin in neonates.

Objectives: CoNS are the most common cause of neonatal late-onset sepsis. Information on the vancomycin pharmacokinetics/pharmacodynamics against CoNS is limited. The aim of this study was to characterize vancomycin pharmacokinetic/pharmacodynamic relationships for CoNS and investigate neonatal optimal dosage regimens.

Clinical pharmacology of antifungal agents in pediatrics: children are not small adults.

The optimal dosage information to improve the prognosis of invasive fungal infections in children and neonates is still limited and current dosing strategies are supported mainly by adult studies and extrapolation. Significant progress has been made to address this need in the last decade. Pre-clinical models and pharmacokinetic-pharmacodynamic (PK-PD) bridging studies supported by pediatric pharmacokinetic studies have investigated optimal dosing regimens for neonates and children.

Pharmacodynamics of fosfomycin: insights into clinical use for antimicrobial resistance.

The aim of this study was to improve the understanding of the pharmacokinetic-pharmacodynamic relationships of fosfomycin against extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli strains that have different fosfomycin MICs. Our methods included the use of a hollow fiber infection model with three clinical ESBL-producing E. coli strains.

Population pharmacokinetics of teicoplanin in children.

Teicoplanin is frequently administered to treat Gram-positive infections in pediatric patients. However, not enough is known about the pharmacokinetics (PK) of teicoplanin in children to justify the optimal dosing regimen. The aim of this study was to determine the population PK of teicoplanin in children and evaluate the current dosage regimens.

Neuroauditory toxicity of artemisinin combination therapies-have safety concerns been addressed?

Although artemisinin-based combination therapies (ACTs) are widely viewed as safe drugs with a wide therapeutic dose range, concerns about neuroauditory safety of artemisinins arose during their development. A decade ago, reviews of human data suggested a potential neuro-ototoxic effect, but the validity of these findings was questioned. With 5-10 years of programmatic use, emerging artemisinin-tolerant falciparum malaria in southeast Asia, and the first calls to consider an increased dose of artemisinins, we review neuroauditory safety data on ACTs to treat uncomplicated falciparum malaria.