Evidence map›Paper›PMID 25773480›Full record

Trial reportClinical pharmacokinetics2015

A Compartmental Analysis for Morphine and Its Metabolites in Young Children After a Single Oral Dose.

Nieves Velez de Mendizabal, Ricardo Jimenez-Mendez, Erin Cooke, Carolyne J Montgomery, Joy Dawes, Michael J Rieder, Katarina Aleksa, Gideon Koren, Carlos O Jacobo-Cabral, Rodrigo Gonzalez-Ramirez and 2 more

Abstract readClinical TrialRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

5 citing papers in PubMed, 15 citations in OpenAlex.

  1. Article
  2. Article
  3. Opioids: A Review of Pharmacokinetics and Pharmacodynamics in Neonates, Infants, and Children.European journal of drug metabolism and pharmacokinetics · 2019
    Review
  4. Review
  5. 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

12 authors at 7 institutions in 3 countries.

Nieves Velez de MendizabalDivision of Clinical Pharmacology, Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
Ricardo Jimenez-MendezDivision of Translational Therapeutics, Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Erin CookePediatric Anesthesia Research Team, University of British Columbia, Vancouver, Canada.
Carolyne J MontgomeryPediatric Anesthesia Research Team, University of British Columbia, Vancouver, Canada.
Joy DawesPediatric Anesthesia Research Team, University of British Columbia, Vancouver, Canada.
Michael J RiederDepartment of Physiology and Pharmacology, Western University, London, Canada.
Katarina AleksaThe Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto, Canada.
Gideon KorenThe Motherisk Program, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, Toronto, Canada.
Carlos O Jacobo-CabralDepartamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico, DF, Mexico.
Rodrigo Gonzalez-RamirezDepartamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico, DF, Mexico.
Gilberto Castañeda-HernandezDepartamento de Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Mexico, DF, Mexico.
Bruce C CarletonDivision of Translational Therapeutics, Department of Paediatrics, Faculty of Medicine, University of British Columbia, Vancouver, Canada. bcarleton@popi.ubc.ca.
Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional · MXBC Children's Hospital · CAHospital for Sick Children · CAUniversity of British Columbia · CAChild and Family Research Institute · CAIndiana Clinical and Translational Sciences Institute · USWestern University · CA

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesCurrently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination with paracetamol (acetaminophen). Codeine is an opioid, which elicits its analgesic effects via metabolism to morphine and codeine-6-glucuronide. Oral morphine is a feasible alternative for outpatient analgesia; however, the pharmacokinetics of morphine after oral administration have been previously described only sparsely, and there is little information in healthy children.

methodsThe clinical trial included 40 children from 2 to 6 years of age, with an American Society of Anaesthesiologists physical status classification of 1 or 2, who were undergoing surgical procedures requiring opioid analgesia. Morphine was orally administered prior to surgery in one of three doses: 0.1 mg/kg, 0.2 mg/kg and 0.3 mg/kg. Blood samples were collected for plasma morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) concentrations at 30, 60, 90, 120, 180 and 240 min after administration. All analyses were performed with the non-linear mixed-effect modelling software NONMEM version 7.2, using the first-order conditional estimation (FOCE) method.

resultsA pharmacokinetic model was developed to simultaneously describe the plasma profiles of morphine and its metabolites M3G and M6G after a single dose of oral morphine in young children (2-6 years of age). The disposition of morphine, M3G and M6G in plasma was best described by a one-compartment model. M3G and M6G metabolite formation was best described by a delay transit compartment, indicating a delay in the appearance of these two major metabolites.

conclusionThis model provides a foundation on which to further evaluate the use of oral morphine and its safety in young children. Longer follow-up time for morphine oral doses and incorporation of other important covariates, such as phenotype, will add value and will help overcome the limitations of the presented population pharmacokinetic analysis.

Indexed as

Administration, OralAnalgesics, OpioidChildChild, PreschoolCodeineCytochrome P-450 CYP2D6FemaleHumansMaleModels, BiologicalMorphineMorphine DerivativesPolymorphism, GeneticPostoperative PainTertiary Care CentersAnalgesics, OpioidCodeinecodeine-6-glucuronideCytochrome P-450 CYP2D6Morphinemorphine-3-glucuronidemorphine-6-glucuronideMorphine Derivatives

Identifiers

PMID25773480
OpenAlexW1980131079

What OpenQuestion holds

Textmetadata
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.