ArticlePharmaceutical research2018
A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered Metabolism of Midazolam Due to Inflammation in Mice.
Article in Pharmaceutical research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed, 7 citations in OpenAlex.
- Determining tissue distribution of the oral antileishmanial agent miltefosine: a physiologically-based pharmacokinetic modeling approach.Antimicrobial agents and chemotherapy · 2024Article
- An exploration on retro-construction of plasma drug concentration-time curves from corresponding urine excretion data and single-point plasma concentrations using a simplified and idealized method.Translational pediatrics · 2023Article
- Potential Effects of COVID-19 on Cytochrome P450-Mediated Drug Metabolism and Disposition in Infected Patients.European journal of drug metabolism and pharmacokinetics · 2021Review
- Variability in Human In Vitro Enzyme Kinetics.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Proteolysis and Oxidation of Therapeutic Proteins After Intradermal or Subcutaneous Administration.Journal of pharmaceutical sciences · 2020Review
- Elucidation of the Differences in Cinobufotalin's Pharmacokinetics Between Normal and Diethylnitrosamine-Injured Rats: The Role of P-Glycoprotein.Frontiers in pharmacology · 2019Article
Corrections and comments
- Erratum issuedCorrection to: A Semi-Physiologically Based Pharmacokinetic Model Describing the Altered Metabolism of Midazolam Due to Inflammation in Mice.2018 · Laird Forrest, M [corrested to Forrest, M Laird]
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
purposeTo investigate influence of inflammation on metabolism and pharmacokinetics (PK) of midazolam (MDZ) and construct a semi-physiologically based pharmacokinetic (PBPK) model to predict PK in mice with inflammatory disease.
methodsGlucose-6-phosphate isomerase (GPI)-mediated inflammation was used as a preclinical model of arthritis in DBA/1 mice. CYP3A substrate MDZ was selected to study changes in metabolism and PK during the inflammation. The semi-PBPK model was constructed using mouse physiological parameters, liver microsome metabolism, and healthy animal PK data. In addition, serum cytokine, and liver-CYP (cytochrome P450 enzymes) mRNA levels were examined.
resultsThe in vitro metabolite formation rate was suppressed in liver microsomes prepared from the GPI-treated mice as compared to the healthy mice. Further, clearance of MDZ was reduced during inflammation as compared to the healthy group. Finally, the semi-PBPK model was used to predict PK of MDZ after GPI-mediated inflammation. IL-6 and TNF-α levels were elevated and liver-cyp3a11 mRNA was reduced after GPI treatment.
conclusionThe semi-PBPK model successfully predicted PK parameters of MDZ in the disease state. The model may be applied to predict PK of other drugs under disease conditions using healthy animal PK and liver microsomal data as inputs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.