PMID- 37714715
OWN - NLM
STAT- Publisher
LR  - 20230915
IS  - 1521-009X (Electronic)
IS  - 0090-9556 (Linking)
DP  - 2023 Sep 15
TI  - Potential and Challenges in Application of Physiologically Based Pharmacokinetic 
      Modeling in Predicting Diarrheal Disease Impact on Oral Drug Pharmacokinetics.
LID - DMD-MR-2022-000964 [pii]
LID - 10.1124/dmd.122.000964 [doi]
AB  - Physiologically based pharmacokinetic (PBPK) modeling is a physiologically 
      relevant approach that integrates drug-specific and system parameters to generate 
      pharmacokinetic predictions for target populations. It has gained immense 
      popularity for drug-drug interaction, organ impairment, and special population 
      studies over the past two decades. However, an application of PBPK modeling with 
      great potential remains rather overlooked - prediction of diarrheal disease 
      impact on oral drug pharmacokinetics. Oral drug absorption is a complex process 
      involving the interplay between physicochemical characteristics of the drug and 
      physiological conditions in the gastrointestinal tract. Diarrhea, a condition 
      common to numerous diseases impacting many worldwide, is associated with 
      physiological changes in many processes critical to oral drug absorption. In this 
      review, we outline key processes governing oral drug absorption, provide a 
      high-level overview of key parameters for modeling oral drug absorption in PBPK 
      models, examine how diarrheal diseases may impact these processes based on 
      literature findings, illustrate the clinical relevance of diarrheal disease 
      impact on oral drug absorption, and discuss the potential and challenges of 
      applying PBPK modeling in predicting disease impacts. Significance Statement 
      Statement Pathophysiological changes resulting from diarrheal diseases can alter 
      important factors governing oral drug absorption, contributing to suboptimal drug 
      exposure and treatment failure. Physiologically based pharmacokinetic (PBPK) 
      modeling is an in silico approach that has been increasingly adopted for 
      drug-drug interaction potential, organ impairment, and special population 
      assessment. This minireview highlights the potential and challenges of using PBPK 
      modeling as a tool to improve our understanding of how diarrheal diseases impact 
      oral drug pharmacokinetics.
CI  - Copyright (c) 2023 American Society for Pharmacology and Experimental Therapeutics.
FAU - Zhang, Cindy X
AU  - Zhang CX
AD  - University of Washington, United States.
FAU - Arnold, Samuel L M
AU  - Arnold SLM
AUID- ORCID: 0000-0001-8290-2347
AD  - University of Washington, United States slarnold@uw.edu.
LA  - eng
PT  - Journal Article
DEP - 20230915
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
SB  - IM
OTO - NOTNLM
OT  - diarrhea
OT  - physiologically-based pharmacokinetic modeling/PBPK
EDAT- 2023/09/16 05:41
MHDA- 2023/09/16 05:41
CRDT- 2023/09/15 21:43
PHST- 2023/08/31 00:00 [accepted]
PHST- 2022/05/30 00:00 [received]
PHST- 2023/08/03 00:00 [revised]
PHST- 2023/09/16 05:41 [medline]
PHST- 2023/09/16 05:41 [pubmed]
PHST- 2023/09/15 21:43 [entrez]
AID - dmd.122.000964 [pii]
AID - 10.1124/dmd.122.000964 [doi]
PST - aheadofprint
SO  - Drug Metab Dispos. 2023 Sep 15:DMD-MR-2022-000964. doi: 10.1124/dmd.122.000964.