Evidence map›Paper›PMID 38164114›Full record

ArticleCPT: pharmacometrics & systems pharmacology2024

Clofazimine pharmacokinetics in HIV-infected adults with diarrhea: Implications of diarrheal disease on absorption of orally administered therapeutics.

Cindy X Zhang, Thomas M Conrad, David Hermann, Melita A Gordon, Eric Houpt, Pui-Ying Iroh Tam, Khuzwayo C Jere, Wilfred Nedi, Darwin J Operario, Jacob Phulusa and 7 more

Open access · goldAbstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

3 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Article
  3. 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

17 authors at 6 institutions in 3 countries.

Cindy X ZhangDepartment of Pharmaceutics, University of Washington, Seattle, Washington, USA.ORCID 0000-0002-0243-7842
Thomas M ConradEmmes, Rockville, Maryland, USA.
David HermannBill & Melinda Gates Foundation, Seattle, Washington, USA.
Melita A GordonPaediatrics and Child Health Research Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Eric HouptDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
Pui-Ying Iroh TamPaediatrics and Child Health Research Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.ORCID 0000-0002-3682-8892
Khuzwayo C JerePaediatrics and Child Health Research Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Wilfred NediPaediatrics and Child Health Research Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.ORCID 0000-0001-8742-8680
Darwin J OperarioDivision of Infectious Diseases and International Health, University of Virginia, Charlottesville, Virginia, USA.
Jacob PhulusaPaediatrics and Child Health Research Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Gerald V QuinnanEmmes, Rockville, Maryland, USA.
Leigh A SawyerEmmes, Rockville, Maryland, USA.
Lynn K BarrettCenter for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
Herbert TholePaediatrics and Child Health Research Group, Malawi-Liverpool Wellcome Trust Clinical Research Programme, Blantyre, Malawi.
Neema TotoLiverpool School of Tropical Medicine, Liverpool, UK.ORCID 0000-0002-9047-217X
Wesley C Van VoorhisCenter for Emerging and Re-emerging Infectious Diseases, University of Washington, Seattle, Washington, USA.
Samuel L M ArnoldDepartment of Pharmaceutics, University of Washington, Seattle, Washington, USA.ORCID 0000-0001-8290-2347
University of Liverpool · GBUniversity of Washington · USEmmes (United States) · USVirginia International University · USGates Foundation · USLiverpool School of Tropical Medicine · GB

Funding

Pharmacokinetic and pharmacodynamic relationships for antibacterial treatment of shigellosisR01AI170784 · NIAID · UNIVERSITY OF WASHINGTON · PI Samuel L Arnold · 2023 to 2026
$1.7M
Gates Foundation OPP1160955Gates Foundation OPP1172544NIAID NIH HHS R01 AI170784
6 · The paper itself

Abstract

Oral drug absorption kinetics are usually established in populations with a properly functioning gastrointestinal tract. However, many diseases and therapeutics can alter gastrointestinal physiology and cause diarrhea. The extent of diarrhea-associated impact on drug pharmacokinetics has not been quantitatively described. To address this knowledge gap, we used a population pharmacokinetic modeling approach with data collected in a phase IIa study of matched human immunodeficiency virus (HIV)-infected adults with/without cryptosporidiosis and diarrhea to examine diarrhea-associated impact on oral clofazimine pharmacokinetics. A population pharmacokinetic model was developed with 428 plasma samples from 23 HIV-infected adults with/without Cryptosporidium infection using nonlinear mixed-effects modeling. Covariates describing cryptosporidiosis-associated diarrhea severity (e.g., number of diarrhea episodes, diarrhea grade) or HIV infection (e.g., viral load, CD4+ T cell count) were evaluated. A two-compartment model with lag time and first-order absorption and elimination best fit the data. Maximum diarrhea grade over the study duration was found to be associated with a more than sixfold reduction in clofazimine bioavailability. Apparent clofazimine clearance, intercompartmental clearance, central volume of distribution, and peripheral volume of distribution were 3.71 L/h, 18.2 L/h (interindividual variability [IIV] 45.0%), 473 L (IIV 3.46%), and 3434 L, respectively. The absorption rate constant was 0.625 h

Indexed as

CryptosporidiosisCryptosporidiumHIV InfectionsAdultClinical Trials, Phase II as TopicClofazimineDiarrheaHIVHumansClofazimine

Identifiers

PMID38164114
PMCPMC10941540
OpenAlexW4390505900

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.