Evidence map›Paper›PMID 34856893›Full record

ArticleCurrent drug metabolism2021

Identification and Quantification of MIDD0301 Metabolites.

M S Rashid Roni, Nicolas M Zahn, Brandon N Mikulsky, Daniel A Webb, Md Yeunus Mian, Daniel E Knutson, Margaret L Guthrie, James M Cook, Douglas C Stafford, Leggy A Arnold

Open access · greenAbstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Current drug metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.2field-weighted citation impact, top 54% 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

2 citing papers in PubMed, 2 citations in OpenAlex.

  1. Article
  2. Article
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

10 authors at 2 institutions in 1 country.

M S Rashid RoniDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
Nicolas M ZahnDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
Brandon N MikulskyPantherics Incorporated, La Jolla, California 92037, United States.
Daniel A WebbDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
Md Yeunus MianDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
Daniel E KnutsonDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
Margaret L GuthrieDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
James M CookDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.
Douglas C StaffordDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States | Pantherics Incorporated, La Jolla, California 92037, United States.
Leggy A ArnoldDepartment of Chemistry and Biochemistry and the Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States | Pantherics Incorporated, La Jolla, California 92037, United States.
University of Wisconsin–Milwaukee · USPanthera Corporation · US

Funding

A novel asthma drug candidate targeting the GABAergic system in lung inflammationR41HL147658 · NHLBI · PANTHERICS INCORPORATED · PI ARNOLD, ALEXANDER · 2019 to 2019
$225k
National Science Foundation, Division of Chemistry CHE-1625735NHLBI NIH HHS R41 HL147658
6 · The paper itself

Abstract

backgroundMIDD0301 is an oral asthma drug candidate that binds GABAA receptors on airway smooth muscle and immune cells.

objectiveThe objective of this study is to identify and quantify MIDD0301 metabolites in vitro and in vivo and determine the pharmacokinetics of oral, IP, and IV administered MIDD0301.

methodsIn vitro conversion of MIDD0301 was performed using liver and kidney microsomes/S9 fractions followed by quantification using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A LC-MS/MS method was developed using synthesized standards to quantify MIDD0301 and its metabolites in urine and feces. Blood, lung, and brain were harvested from animals that received MIDD0301 by oral, IP, and IV administration, followed by LCMS/ MS quantification. Imaging mass spectrometry was used to demonstrate the presence of MIDD0301 in the lung after oral administration.

resultsMIDD0301 is stable in the presence of liver and kidney microsomes and S9 fractions for at least two hours. MIDD0301 undergoes conversion to the corresponding glucuronide and glucoside in the presence of conjugating cofactors. For IP and IV administration, unconjugated MIDD0301 together with significant amounts of MIDD0301 glucoside and MIDD0301 taurine were found in urine and feces. Less conjugation was observed following oral administration, with MIDD0301 glucuronide being the main metabolite. Pharmacokinetic quantification of MIDD0301 in blood, lung, and brain showed very low levels of MIDD0301 in the brain after oral, IV, or IP administration. The drug half-life in these tissues ranged between 4-6 hours for IP and oral and 1-2 hours for IV administration. Imaging mass spectrometry demonstrated that orally administered MIDD0301 distributes uniformly in the lung parenchyma.

conclusionMIDD0301 undergoes no phase I and moderate phase II metabolism.

Indexed as

Administration, IntravenousAdministration, OralAnimalsAnti-Asthmatic AgentsAzepinesChromatography, LiquidDogsFemaleHumansImidazolesInjections, IntraperitonealKidneyLungMiceMicrosomesMicrosomes, LiverAnti-Asthmatic AgentsAzepinesImidazolesMIDD0301GABAA receptor.glucosidationglucuronidationimaging mass spectrometrymetabolismMIDD0301taurine conjugate

Identifiers

PMID34856893
PMCPMC8760168
OpenAlexW3217573369

What OpenQuestion holds

Textmetadata
LicenceTDM
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 OpenQuestion graph.