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Record W1970521541 · doi:10.1211/jpp.59.8.0004

Central nervous system distribution kinetics of indinavir in rats

2007· article· en· W1970521541 on OpenAlexfundno aff
Mehrdad Hamidi

Bibliographic record

VenueJournal of Pharmacy and Pharmacology · 2007
Typearticle
Languageen
FieldMedicine
TopicDrug Transport and Resistance Mechanisms
Canadian institutionsnot available
FundersUniversity of Toronto
KeywordsIndinavirCerebrospinal fluidParenchymaPharmacokineticsChemistryCentral nervous systemDistribution (mathematics)EffluxBlood–brain barrierChromatographyKineticsIn vivoPharmacologyBlood plasmaInternal medicineMedicinePathologyBiologyImmunologyHuman immunodeficiency virus (HIV)BiochemistrySida

Abstract

fetched live from OpenAlex

The central nervous system (CNS) distribution kinetics of indinavir were extensively evaluated using a combinational in-vivo model comprising the integration plot method (a single-passage approach) and neuropharmacokinetic method (a multiple-passage approach). A 5 mg kg(-1) dose of indinavir was administered intravenously to rats. Blood and cerebrospinal fluid (CSF) samples and whole brain were collected from the animals at specified time points and the drug concentration in each sample was determined using a high-performance liquid chromatography method. For the neuropharmacokinetic study, the simultaneous plasma, CSF and brain concentrations were fitted to an integrated model, which resulted in the estimation of the influx (K(in)) and efflux (K(out)) rate constants of the drug to/from CSF and brain parenchyma. The integration plot method involved plotting the brain-plasma or CSF-plasma concentration ratios (K(p, app)) against AUC(0-->t)/C(p(t)), and estimating the uptake clearance of the drug by brain/CSF from the slope of the initial linear portion of the plot. The K(in) and K(out) values of the drug to/from CSF were estimated to be 2.42 x 10(-2) and 13.26 x 10(-2)min(-1), respectively, and the corresponding values for brain parenchyma were 1.02 x 10(-2) and 1.32 x 10(-2) min(-1), respectively. The uptake clearances of indinavir by CSF and brain parenchyma were 8.89 and 8.38microL min(-1)g(-1), respectively. The permeability surface area products of the drug for the blood-brain barrier and blood-CSF barrier were estimated as 1.05 x 10(-2) and 2.45 x 10(-2) mLmin(-1)g(-1), respectively. The estimated kinetic parameters indicated limited CNS entry of the drug because of the limited blood-brain barrier permeability and the efficient drug efflux from CNS, particularly from CSF.

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: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.051
Threshold uncertainty score0.335

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
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 head0.015
GPT teacher head0.317
Teacher spread0.302 · 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 designBench or experimental
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

Citations9
Published2007
Admission routes1
Has abstractyes

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