A gaveta da memória

Franchetti, Paulo

doi:10.1590/s0103-73072008000100010

Cited by 1 publication

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“…We have developed a top-down plus bottom-up or "middle-out" PBPK approach, namely, individualized PBPK modeling of rate data (iPBPK-R) using a reduced-order model and applied it to 14 CO 2 production rate data. 87,88 Figure 1 contrasts the middleout iPBPK-R approach with general bottom-up PBPK approaches. 89 iPBPK-R enables the simultaneous evaluation of hepatic transport and metabolism pathways and exploration of uremic toxin-mediated alterations of drug disposition in individuals.…”

Section: A Middle-out Pbpk Approach To Simultaneously Evaluate Hepatimentioning

confidence: 99%

Dose Optimization in Kidney Disease: Opportunities for PBPK Modeling and Simulation

Franchetti

Nolin

2020

The Journal of Clinical Pharma

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Kidney disease affects pharmacokinetic (PK) profiles of not only renally cleared drugs but also nonrenally cleared drugs. The impact of kidney disease on drug disposition has not been fully elucidated, but describing the extent of such impact is essential for conducting dose optimization in kidney disease. Accurate evaluation of kidney function has been a clinical interest for dose optimization, and more scientists pay attention and conduct research for clarifying the role of drug transporters, metabolic enzymes, and their interplay in drug disposition as kidney disease progresses. Physiologically based pharmacokinetic (PBPK) modeling and simulation can provide valuable insights for dose optimization in kidney disease. It is a powerful tool to integrate discrete knowledge from preclinical and clinical research and mechanistically investigate system-and drug-dependent factors that may contribute to the changes in PK profiles. PBPK-based prediction of drug exposures may be used a priori to adjust dosing regimens and thereby minimize the likelihood of drug-related toxicity. With real-time clinical studies, parameter estimation may be performed with PBPK approaches that can facilitate identification of sources of interindividual variability. PBPK modeling may also facilitate biomarker research that aids dose optimization in kidney disease. U.S. Food and Drug Administration guidances related to conduction of PK studies in kidney impairment and PBPK documentation provide the foundation for facilitating model-based dose-finding research in kidney disease.

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Section: A Middle-out Pbpk Approach To Simultaneously Evaluate Hepatimentioning

confidence: 99%