To Estimate or to Forecast? Lessons From a Comparative Analysis of Four Bayesian Fitting Methods Based on Nonparametric Models.

Using pharmacokinetic (PK) models and Bayesian methods in dosing software facilitates the analysis of individual PK data and precision dosing. Several Bayesian methods are available for computing Bayesian posterior distributions using nonparametric population models. The objective of this study was to compare the performance of the maximum a posteriori (MAP) model, multiple model (MM), interacting MM (IMM), and novel hybrid MM(HMM) in estimating past concentrations and predicting future concentrations during therapy.

An Algorithm for Nonparametric Estimation of a Multivariate Mixing Distribution with Applications to Population Pharmacokinetics.

Population pharmacokinetic (PK) modeling has become a cornerstone of drug development and optimal patient dosing. This approach offers great benefits for datasets with sparse sampling, such as in pediatric patients, and can describe between-patient variability. While most current algorithms assume normal or log-normal distributions for PK parameters, we present a mathematically consistent nonparametric maximum likelihood (NPML) method for estimating multivariate mixing distributions without any assumption about the shape of the distribution.

Prospective Trial on the Use of Trough Concentration versus Area under the Curve To Determine Therapeutic Vancomycin Dosing.

We hypothesized that dosing vancomycin to achieve trough concentrations of >15 mg/liter overdoses many adults compared to area under the concentration-time curve (AUC)-guided dosing. We conducted a 3-year, prospective study of vancomycin dosing, plasma concentrations, and outcomes. In year 1, nonstudy clinicians targeted trough concentrations of 10 to 20 mg/liter (infection dependent) and controlled dosing.

Accurately Achieving Target Busulfan Exposure in Children and Adolescents With Very Limited Sampling and the BestDose Software.

Background: Busulfan dose adjustment is routinely guided by plasma concentration monitoring using 4-9 blood samples per dose adjustment, but a pharmacometric Bayesian approach could reduce this sample burden.

Methods: The authors developed a nonparametric population model with Pmetrics. They used it to simulate optimal initial busulfan dosages, and in a blinded manner, they compared dosage adjustments using the model in the BestDose software to dosage adjustments calculated by noncompartmental estimation of area under the time-concentration curve at a national reference laboratory in a cohort of patients not included in model building.

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.