Evidence map›Paper›PMID 29494403›Full record

ArticleAnesthesiology2018

Pharmacokinetic/Pharmacodynamic Model of CW002, an Investigational Intermediate Neuromuscular Blocking Agent, in Healthy Volunteers.

Josh D Kaullen, Joel S Owen, Kim L R Brouwer, Paul M Heerdt, Cynthia A Lien, John J Savarese, Virginia D Schmith

Abstract read
In one paragraph

Article in Anesthesiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.6field-weighted citation impact, top 32% 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.

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

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Narrative Review of the Role of Nondepolarizing Neuromuscular Blocking Agents in Anesthesia: Perspective 2026.Medical science monitor : international medical journal of experimental and clinical research · 2026
    Review
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

7 authors at 1 institution in 2 countries.

Josh D KaullenFrom the Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (J.D.K., K.L.R.B.) Union University, Jackson, Tennessee (J.S.O.) Yale Medical School, New Haven, Connecticut (P.M.H.) Weill Cornell Medical College, New York, New York (C.A.L., J.J.S.) Nuventra Pharma Sciences, Durham, North Carolina (V.D.S.).
Joel S Owen
Kim L R Brouwer
Paul M Heerdt
Cynthia A Lien
John J Savarese
Virginia D Schmith
University of North Carolina at Chapel Hill · US

Funding

ALTERED HEPATIC DISPOSITION OF ANIONIC DRUGS-MECHANISMSR01GM041935 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BROUWER, KIM L.R. · 1997 to 2016
$6.5M
Mechanisms of Altered Hepatic Transport: Impact on Drug TherapyR35GM122576 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KIM L.R. BROUWER · 2017 to 2026
$5.7M
NIGMS NIH HHS R01 GM041935NIGMS NIH HHS R35 GM122576
6 · The paper itself

Abstract

backgroundCW002 is an investigational nondepolarizing, neuromuscular blocking agent with a rapid onset and intermediate duration of action in animals. This is a single ascending dose, healthy subject study exploring tolerability, pharmacokinetics, and potency.

methodsPopulation pharmacokinetic and pharmacokinetic/pharmacodynamic models were developed using plasma drug concentration data from a previously published dose-response study in 28 healthy subjects receiving single doses of CW002 during sevoflurane anesthesia. Subjects included in the models were from five different dose cohorts (cohorts 3, 4, 5, 6, and 8 receiving 0.04, 0.06, 0.08, 0.10, and 0.14 mg/kg, respectively). Serial arterial plasma concentrations and muscle twitch heights were monitored.

resultsA four-compartment model was fit to the concentration-time data, whereas a transit compartment with a sigmoid Emax model was fit to the pharmacokinetic/pharmacodynamic data. The population pharmacokinetics of CW002 was linear with very low interindividual variability in clearance (10.8%). Simulations were conducted to predict the onset and offset of effect at 2×, 3×, and 4× ED95. The time to 80% block was predicted to be 1.5, 0.8, and 0.7 min for 2×, 3×, and 4× ED95 doses, respectively. The simulated 25 to 75% recovery index was independent of dose.

conclusionsCW002 has predictable pharmacokinetics and is likely to have a rapid onset with an intermediate duration of action at 3× ED95. This model provides information to inform critical decisions (e.g., dose, study design) for continued development of CW002.

Indexed as

Models, BiologicalAdolescentAdultCohort StudiesFemaleHealthy VolunteersHumansIsoquinolinesMaleMiddle AgedNeuromuscular Blocking AgentsYoung AdultCW 002IsoquinolinesNeuromuscular Blocking Agents

Identifiers

PMID29494403
PMCPMC5953789
OpenAlexW2788446773

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.