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Record W2606334551 · doi:10.1002/cpdd.358

Single‐ and Multiple‐Dose Pharmacokinetics of Once‐Daily Formulations of Raltegravir

2017· article· en· W2606334551 on OpenAlexaff
Rajesh Krishna, Matthew L. Rizk, Patrick Larson, Valerie Schulz, Filippos Kesisoglou, Radu Pop

Bibliographic record

VenueClinical Pharmacology in Drug Development · 2017
Typearticle
Languageen
FieldMedicine
TopicHIV/AIDS drug development and treatment
Canadian institutionsPharma Medica Research (Canada)
FundersMerck
KeywordsRaltegravirPharmacokineticsBioavailabilityPharmacologyMedicineBiopharmaceuticsDosingBiopharmaceutics Classification SystemIn vivoHuman immunodeficiency virus (HIV)ChemistryVirologyAntiretroviral therapyIn vitroBiological activityBiologyViral loadBiochemistryPharmacognosyBiotechnology

Abstract

fetched live from OpenAlex

Abstract A new once‐daily formulation of raltegravir, an integrase strand transfer inhibitor indicated in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus–1 infection, is under development. Single‐dose and steady‐state pharmacokinetics of 1200 mg for 2 formulations of raltegravir were characterized in 2 open‐label phase 1 studies in healthy male and female subjects aged 18 to 55 years. The new raltegravir 600‐mg formulation had a higher relative bioavailability compared with the 400‐mg tablets. Once absorbed, both 3 × 400‐mg and 2 × 600‐mg dosage forms of raltegravir exhibited similar systemic pharmacokinetics; in dictating bioavailability, differences were from increased absorption that was the result of improved in vivo disintegration/dissolution. Food had a smaller effect on the pharmacokinetics of raltegravir when given as 2 × 600‐mg formulation (42% vs 73% decrease in AUC 0–last ). Steady state was generally reached in 2 days, with little to no accumulation with multiple‐dose administration. Raltegravir 1200 mg was found to exhibit pharmacokinetic properties amenable for once‐daily dosing and was generally well tolerated in healthy subjects after single and multiple doses. The new formulation improved the bioavailability of this Biopharmaceutics Classification System class II compound.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.092
Threshold uncertainty score0.866

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
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 head0.085
GPT teacher head0.417
Teacher spread0.332 · 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.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

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

Citations27
Published2017
Admission routes1
Has abstractyes

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