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Record W2092729209 · doi:10.1177/0091270007306957

Pharmacokinetic Profile of Temsirolimus With Concomitant Administration of Cytochrome P450‐Inducing Medications<sup>1</sup>

2007· article· en· W2092729209 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueThe Journal of Clinical Pharmacology · 2007
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCancer therapeutics and mechanisms
Canadian institutionsWomen's Health Research Institute
Fundersnot available
KeywordsTemsirolimusPharmacologySirolimusCYP3A4PharmacokineticsCYP3AConcomitantMedicineCytochrome P450Internal medicineChemistryDiscovery and development of mTOR inhibitorsPI3K/AKT/mTOR pathwayBiochemistryMetabolism

Abstract

fetched live from OpenAlex

Temsirolimus is a novel inhibitor of the mammalian target of rapamycin, with antitumor activity in advanced tumors. Because temsirolimus and its metabolite, sirolimus, are cytochrome P450 (CYP) 3A4/5 substrates, the potential exists for interaction with drugs that induce CYP3A activity, including enzyme inducers and rifampin. Cancer patients received once-weekly intravenous (IV) 220 mg/m(2) temsirolimus with or without enzyme inducers. Coadministration with enzyme inducers decreased temsirolimus maximum plasma concentration (C(max)) by 36% and increased volume of distribution by 99%. Sirolimus C(max) and area under the concentration-time curve (AUC) were decreased by 67% and 43%, respectively. In healthy adult subjects, coadministration of 25-mg intravenous temsirolimus with rifampin had no significant effect on temsirolimus C(max) and AUC but decreased sirolimus C(max) and AUC by 65% and 56%, respectively. Rifampin decreased AUC(sum) by 41%. Temsirolimus was well tolerated in both studies. If concomitant agents with CYP3A induction potential are used, higher temsirolimus doses may be needed to achieve adequate tumor tissue drug levels.

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.

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)0.003
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.014
Threshold uncertainty score0.331

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0030.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
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 head0.038
GPT teacher head0.402
Teacher spread0.365 · 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