Evidence map›Paper›PMID 26852745›Full record

Trial reportBritish journal of clinical pharmacology2016

Identifying 24 h variation in the pharmacokinetics of levofloxacin: a population pharmacokinetic approach.

Laura Kervezee, Jasper Stevens, Willem Birkhoff, Ingrid M C Kamerling, Theo de Boer, Melloney Dröge, Johanna H Meijer, Jacobus Burggraaf

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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

13 citing papers in PubMed.

  1. Trial
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  8. Review
  9. The power of modelling pulsatile profiles.Journal of pharmacokinetics and pharmacodynamics · 2021
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  11. Review
  12. Article
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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

8 authors.

Laura KervezeeLaboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden.
Jasper StevensCentre for Human Drug Research, Leiden.
Willem BirkhoffCentre for Human Drug Research, Leiden.
Ingrid M C KamerlingCentre for Human Drug Research, Leiden.
Theo de BoerABL Laboratories, Assen, the Netherlands.
Melloney DrögeABL Laboratories, Assen, the Netherlands.
Johanna H MeijerLaboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden University Medical Center, Leiden.
Jacobus BurggraafCentre for Human Drug Research, Leiden.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimThe objective of this study was to investigate whether the pharmacokinetics of orally administered levofloxacin show 24 h variation. Levofloxacin was used as a model compound for solubility and permeability independent absorption and passive renal elimination.

methodsIn this single centre, crossover, open label study, 12 healthy subjects received an oral dose of 1000 mg levofloxacin at six different time points equally divided over the 24 h period. Population pharmacokinetic modelling was used to identify potential 24 h variation in the pharmacokinetic parameters of this drug.

resultsThe pharmacokinetics of levofloxacin could be described by a one compartment model with first order clearance and a transit compartment to describe drug absorption. The fit of the model was significantly improved when the absorption rate constant was described as a cosine function with a fixed period of 24 h, a relative amplitude of 47% and a peak around 08.00 h in the morning. Despite this variation in absorption rate constant, simulations of a once daily dosing regimen showed that tmax , Cmax and the area under the curve at steady-state were not affected by the time of drug administration.

conclusionThe finding that the absorption rate constant showed considerable 24 h variation may be relevant for drugs with similar physicochemical properties as levofloxacin that have a narrower therapeutic index. Levofloxacin, however, can be dosed without taking into account the time of day, at least in terms of its pharmacokinetics.

Indexed as

Circadian RhythmModels, BiologicalAdministration, OralAdolescentAdultAnti-Bacterial AgentsComputer SimulationCross-Over StudiesDose-Response Relationship, DrugElectrocardiographyGlomerular Filtration RateHumansLevofloxacinMaleMiddle AgedThyrotropinAnti-Bacterial AgentsLevofloxacinThyrotropinchronopharmacokineticsdiurnal variationfluoroquinolonepopulation pharmacokinetic modellingtime of administration

Identifiers

PMID26852745
PMCPMC4833164

What OpenQuestion holds

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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.