PBPK Modeling and Simulation and Therapeutic Drug Monitoring: Possible Ways for Antibiotic Dose Adjustment

Abstract

Pharmacokinetics (PK) is a branch of pharmacology present and of vital importance for the research and development (R&D) of new drugs, post-market monitoring, and continued optimizations in clinical contexts. Ultimately, pharmacokinetics can contribute to improving patients’ clinical outcomes, helping enhance the efficacy of treatments, and reducing possible adverse side effects while also contributing to precision medicine. This article discusses the methods used to predict and study human pharmacokinetics and their evolution to the current physiologically based pharmacokinetic (PBPK) modeling and simulation methods. The importance of therapeutic drug monitoring (TDM) and PBPK as valuable tools for Model-Informed Precision Dosing (MIPD) are highlighted, with particular emphasis on antibiotic therapy since dosage adjustment of antibiotics can be vital to ensure successful clinical outcomes and to prevent the spread of resistant bacterial strains.

Semi-Automated Therapeutic Drug Monitoring as a Pillar toward Personalized Medicine for Tuberculosis Management

“…Another possible approach known as mechanistic MIPD has been proposed [ 4 ]. In recent years, the capacity of physiologically based pharmacokinetics (PBPK) modeling to evaluate physiological covariates associated with variability in drug exposure has gained attention [ 95 , 96 ]. PBPK models can be used for various purposes and applications and present numerous advantages compared to other methods [ 96 , 97 ].…”

“…PBPK models can be used for various purposes and applications and present numerous advantages compared to other methods [ 96 , 97 ]. PBPK models incorporate physiological data from preclinical species, aid in allometric scaling, can be parametrized for specific individuals or populations, and account for sequential metabolism- and permeability-constrained processes [ 95 , 97 , 98 ]. PBPK is a promising tool that may help apply more precise MIPD to edge populations.…”

“…This study showed that PBPK has the potential to eventually be adapted in the clinical use of TDM. In advance, PBPK and population PK have been used as a combined approach in several complimentary confirmation studies [ 95 , 100 , 101 ]. As far as we are concerned, PBPK can also be combined with population PK to implement Bayesian forecasting (middle-out approach).…”

Therapeutic target mapping from the genome of Kingella negevensis and biophysical inhibition assessment through PNP synthase binding with traditional medicinal compounds

“…For this purpose, the absorption, distribution, metabolism, and excretion (ADME) properties, along with physiologically based pharmacokinetic (PBPK) profiling helps confirm drug efficacy and tolerability [ 16 ]. In the past, poor PK properties (e.g., small bioavailability) have led to the failure of a large fraction of lead compounds [ 17 ]. This is why, good PK properties can be of motivation to further explore molecule as a drug.…”

Population Pharmacokinetic Modeling of Zaltoprofen in Healthy Adults: Exploring the Dosage Regimen

“…Pharmacokinetic variability within a group and drug modeling studies are useful scientific approaches to reducing side effects and maximizing drug efficacy by finding effective dosages based on quantitative predictions [ 14 , 15 , 16 ]. The purpose of this study was to perform population pharmacokinetic (PPK) modeling of zaltoprofen and discover effective covariates affecting interindividual pharmacokinetic variability.…”