Evidence map›Paper›PMID 36972999›Full record

ArticleDrug metabolism and disposition: the biological fate of chemicals2023

A Physiologically-Based Pharmacokinetic Model for Cannabidiol in Healthy Adults, Hepatically-Impaired Adults, and Children.

Sumit Bansal, Mayur K Ladumor, Mary F Paine, Jashvant D Unadkat

Open access · greenAbstract read
In one paragraph

Article in Drug metabolism and disposition: the biological fate of chemicals, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
4.1field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.

  1. Does acute cannabidiol (CBD) use impair performance? A meta-analysis and comparison with placebo and delta-9-tetrahydrocannabinol (THC).Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
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  13. Advances and Challenges in Modeling Cannabidiol Pharmacokinetics and Hepatotoxicity.Drug metabolism and disposition: the biological fate of chemicals · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Sumit BansalDepartment of Pharmaceutics, University of Washington, Seattle, Washington (S.B., M.K.L., J.D.U.); Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (M.F.P.); and Center of Excellence for Natural Product Drug Interaction Research (M.F.P., J.D.U.).
Mayur K LadumorDepartment of Pharmaceutics, University of Washington, Seattle, Washington (S.B., M.K.L., J.D.U.); Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (M.F.P.); and Center of Excellence for Natural Product Drug Interaction Research (M.F.P., J.D.U.).ORCID 0000-0003-2632-8525
Mary F PaineDepartment of Pharmaceutics, University of Washington, Seattle, Washington (S.B., M.K.L., J.D.U.); Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (M.F.P.); and Center of Excellence for Natural Product Drug Interaction Research (M.F.P., J.D.U.).ORCID 0000-0002-3331-1839
Jashvant D UnadkatDepartment of Pharmaceutics, University of Washington, Seattle, Washington (S.B., M.K.L., J.D.U.); Department of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (M.F.P.); and Center of Excellence for Natural Product Drug Interaction Research (M.F.P., J.D.U.) jash@uw.edu.ORCID 0000-0002-4820-8455
Washington State University Spokane · US

Funding

Pharmacology CoreU54AT008909 · NCCIH · WASHINGTON STATE UNIVERSITY · PI PAINE, MARY F · 2015 to 2024
$22.4M
Understanding Fetal Exposure to Cannabinoids Through In Vitro and In Vivo StudiesP01DA032507 · NIDA · UNIVERSITY OF WASHINGTON · PI UNADKAT, JASHVANT D · 2013 to 2023
$12.4M
Mechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder P50HD103524 · NICHD · UNIVERSITY OF WASHINGTON · PI Sandra E Juul · 2020 to 2026
$9.9M
NCCIH NIH HHS U54 AT008909NICHD NIH HHS P50 HD103524NIDA NIH HHS P01 DA032507
6 · The paper itself

Abstract

Cannabidiol (CBD) is available as a prescription oral drug that is indicated for the treatment of some types of epilepsy in children and adults. CBD is also available over-the-counter and is used to self-treat a variety of other ailments, including pain, anxiety, and insomnia. Accordingly, CBD may be consumed with other medications, resulting in possible CBD-drug interactions. Such interactions can be predicted in healthy and hepatically-impaired (HI) adults and in children through physiologically based pharmacokinetic (PBPK) modeling and simulation. These PBPK models must be populated with CBD-specific parameters, including the enzymes that metabolize CBD in adults. In vitro reaction phenotyping experiments showed that UDP-glucuronosyltransferases (UGTs, 80%), particularly UGT2B7 (64%), were the major contributors to CBD metabolism in adult human liver microsomes. Among the cytochrome P450s (CYPs) tested, CYP2C19 (5.7%) and CYP3A (6.5%) were the major CYPs responsible for CBD metabolism. Using these and other physicochemical parameters, a CBD PBPK model was developed and validated for healthy adults. This model was then extended to predict CBD systemic exposure in HI adults and children. Our PBPK model successfully predicted CBD systemic exposure in both populations within 0.5- to 2-fold of the observed values. In conclusion, we developed and validated a PBPK model to predict CBD systemic exposure in healthy and HI adults and children. This model can be used to predict CBD-drug or CBD-drug-disease interactions in these populations. SIGNIFICANCE STATEMENT: Our PBPK model successfully predicted CBD systemic exposure in healthy and hepatically-impaired adults, as well as children with epilepsy. This model could be used in the future to predict CBD-drug or CBD-drug-disease interactions in these special populations.

Indexed as

CannabidiolAdultChildCytochrome P-450 Enzyme SystemDrug InteractionsHumansMicrosomes, LiverModels, BiologicalCannabidiolCytochrome P-450 Enzyme System

Identifiers

PMID36972999
PMCPMC10197200
OpenAlexW4361018581

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.