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Record W1963760050 · doi:10.2133/dmpk.dmpk-12-rv-099

Impact of Genetic Variation in OATP Transporters to Drug Disposition and Response

2012· review· en· W1963760050 on OpenAlexaff
Inna Y. Gong, Richard B. Kim

Bibliographic record

VenueDrug Metabolism and Pharmacokinetics · 2012
Typereview
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsWestern University
Fundersnot available
KeywordsOrganic anion-transporting polypeptideTransporterDrugPharmacologySLCO1B1Organic anion transporter 1Solute carrier familyPharmacokineticsBiologyPharmacodynamicsPharmacogeneticsBiochemistryGeneGenotype

Abstract

fetched live from OpenAlex

There has been remarkable progress during the past decade in understanding of how genetic variations in drug metabolizing enzymes and transporters contribute to observed variation in drug responsiveness. Among drug transporters, the organic anion transporting polypeptide (OATP) class of transporters have proven to be remarkably important to the cellular uptake disposition of a variety of clinically important drugs, particularly in organs such as the intestine and liver; we now know that altered OATP activity may confer reduced efficacy and potentially increased risk of drug-related toxicity. OATP1B1 and OATP1B3 are widely recognized liver-specific members of the family known to modulate the hepatocellular uptake of drugs from the portal vein and thereby modulate systemic exposure and hepatic substrate drug extraction. On the other hand, OATP2B1 and OATP1A2 are expressed on the apical membrane of intestinal enterocytes and though to affect absorption of its drug substrates. Accordingly, genetic variations in these OATP transporters have clinically relevant functional consequences for drug absorption, distribution and excretion, as well as pharmacodynamics response in terms of drug efficacy and toxicity. This article addresses the present evidence of relevance to genetic variations in OATP1B1, OATP1B3, OATP2B1, and OATP1A2 in terms of drug response, efficacy and optimal therapeutics.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Other design · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.966
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0020.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.023
GPT teacher head0.330
Teacher spread0.308 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

Study designOther design
Domainnot available
GenreReview

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations134
Published2012
Admission routes1
Has abstractyes

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