Evidence map›Paper›PMID 30054895›Full record

Trial reportDrugs in R&D2018

Population Pharmacokinetic Modelling of Ceftazidime and Avibactam in the Plasma and Epithelial Lining Fluid of Healthy Volunteers.

Richard Dimelow, James G Wright, Merran MacPherson, Paul Newell, Shampa Das

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in Drugs in R&D, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01395420 (A Phase I Open-Label, 2-Part, 3-Cohort, Single-Centre Study to Assess the Concentration of Avibactam and Ceftazidime in Epithelial Lining Fluid), which is not on this map. Cited by 36 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 2 pooled it
2.5field-weighted citation impact, top 11% of its field
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.

NCT01395420 phase1completednot on this map

A Phase I Open-Label, 2-Part, 3-Cohort, Single-Centre Study to Assess the Concentration of Avibactam and Ceftazidime in Epithelial Lining Fluid (ELF) and Plasma Using at Least Two Different Dosing Regimens in Healthy Volunteers

TypeinterventionalSponsorPfizerRan2011 to 2012Enrolled45ConditionsHealthyArmsCAZ104
3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 2 syntheses or guidelines pooled it, 48 citations in OpenAlex.

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  12. Towards a holistic approach to pulmonary infections. Insights from the Sixth Annual Meeting of Spanish Experts 2024.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2025
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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

5 authors at 2 institutions in 1 country.

Richard DimelowWright Dose Ltd, Altrincham, Cheshire, UK.
James G WrightWright Dose Ltd, Altrincham, Cheshire, UK.
Merran MacPhersonWright Dose Ltd, Altrincham, Cheshire, UK.
Paul NewellAstraZeneca Global Medicines Development, Alderley Park, Macclesfield, Cheshire, UK.
Shampa DasAstraZeneca Global Medicines Development, Alderley Park, Macclesfield, Cheshire, UK. shampa.das@liverpool.ac.uk.ORCID http://orcid.org/0000-0002-2540-4816
AstraZeneca (United Kingdom) · GBGlaxoSmithKline (United Kingdom) · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesOur objective was to develop population pharmacokinetic (PK) models for ceftazidime and avibactam in the plasma and epithelial lining fluid (ELF) of healthy volunteers and to compare ELF concentrations to plasma PK/pharmacodynamic (PD) targets.

methodsPlasma and ELF population PK models were developed for ceftazidime and avibactam concentration data from 42 subjects (NCT01395420). Two- and three-compartment plasma PK models were fitted to ceftazidime and avibactam plasma PK data, and different plasma-ELF linked models were evaluated. Using best-fitting models, plasma and ELF concentration-time profiles were simulated for 1000 subjects. ELF concentration-time profiles for ceftazidime/avibactam 2000-500 mg every 8 h were compared with plasma PK/PD targets for ceftazidime (50% of time above [fT >] 8 mg/l) and avibactam (50% fT > 1 mg/l).

resultsThree-compartment PK models best fitted the plasma concentration data for ceftazidime and avibactam. ELF data for both drugs were best described by a direct response (instantaneous equilibrium) model. Ceftazidime plasma-ELF relationships were best described by a saturable Michaelis-Menten model. For avibactam, departure from plasma-ELF relationship linearity was more modest than for ceftazidime. ELF:plasma penetration ratios of both ceftazidime (52%) and avibactam (42%) at plasma concentrations relevant for efficacy (~ 8 mg/l for ceftazidime and ~ 1 mg/l for avibactam) were greater than previously calculated using non-compartmental area under the curve (AUC) methods, which average across the entire concentration range. Ceftazidime and avibactam ELF exposures exceeded their respective plasma PK/PD time-above-threshold targets by the dosing interval mid-point in most subjects.

conclusionsThis compartmental modelling analysis suggests ELF exposures of both ceftazidime and avibactam exceed levels required for efficacy in plasma.

Indexed as

Healthy VolunteersModels, BiologicalAzabicyclo CompoundsBronchoalveolar Lavage FluidCeftazidimeHumansInfusions, IntravenousMaleavibactamAzabicyclo CompoundsCeftazidime

Identifiers

PMID30054895
PMCPMC6131119
OpenAlexW2883761563

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

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.