Optimizing Clinical Outcomes Through Rational Dosing Strategies: Roles of Pharmacokinetic/Pharmacodynamic Modeling Tools

Abstract

Significant progress in previous decades has led to several methodologies developed to facilitate the design of optimal antimicrobial dosing. In this review, we highlight common pharmacokinetic/pharmacodynamic (PKPD) modeling techniques and their roles in guiding rational dosing regimen design. In the early drug development phases, dose fractionation studies identify the PKPD index most closely associated with bacterial killing. Once discerned, this index is linked to clinical efficacy end points, and classification and regression tree analysis can be used to define the PKPD target goal. Monte Carlo simulations integrate PKPD and microbiological data to identify dosing strategies with a high probability of achieving the established PKPD target. Results then determine dosing regimens to investigate and/or validate the findings of randomized controlled trials. Further improvements in PKPD modeling could lead to an era of precision dosing and personalized therapeutics.

Effective Antimicrobial Prophylaxis in Surgery: The Relevance and Role of Pharmacokinetics-Pharmacodynamics

“…Monto Carlo simulation studies are important in antimicrobial PKPD research and knowledge translation [12,48]. They can integrate the complexity of numerous and often interdependent variables related to the patient, antibiotic, and infection.…”

Optimizing tylosin dosage for co-infection of Actinobacillus pleuropneumoniae and Pasteurella multocida in pigs using pharmacokinetic/pharmacodynamic modeling

“…This model involves equations that relate the drug concentration in the body to the observed response, such as changes in blood pressure or inhibition of bacterial growth ( Bauer and Bauer, 2008 ). To evaluate the likelihood of achieving the desired pharmacological response for a given drug dosing plan, PK/PD modeling uses the Monte Carlo Simulation, a powerful computational technique ( Chua and Tam, 2022 ). The Probability of Target Attainment (PTA) is a vital concept in this analysis, as it helps assess the drug’s effectiveness and predictability ( Cristinacce et al, 2019 ).…”