Evidence map›Paper›PMID 27815868›Full record

Trial reportClinical pharmacokinetics2017

A Prospective Population Pharmacokinetic Study on Morphine Metabolism in Cancer Patients.

Astrid W Oosten, João A Abrantes, Siv Jönsson, Maja Matic, Ron H N van Schaik, Peter de Bruijn, Carin C D van der Rijt, Ron H J Mathijssen

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in Clinical pharmacokinetics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.4field-weighted citation impact, top 17% 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

7 citing papers in PubMed, 21 citations in OpenAlex.

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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 at 5 institutions in 2 countries.

Astrid W OostenDepartment of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands. a.oosten@erasmusmc.nl.
João A AbrantesDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Siv JönssonDepartment of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
Maja MaticDepartment of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands.
Ron H N van SchaikDepartment of Clinical Chemistry, Erasmus MC, Rotterdam, The Netherlands.
Peter de BruijnDepartment of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
Carin C D van der RijtDepartment of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
Ron H J MathijssenDepartment of Medical Oncology, Erasmus MC Cancer Institute, Groene Hilledijk 301, 3075 EA, Rotterdam, The Netherlands.
Erasmus MC Cancer Institute · NLUppsala University · SEErasmus MC · NLErasmus MC - Sophia Children’s Hospital · NLNetherlands Comprehensive Cancer Organisation · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundOral and subcutaneous morphine is widely used for the treatment of cancer-related pain; however, solid pharmacokinetic data on this practice are lacking. Furthermore, it is largely unknown which factors contribute to the variability in clearances of morphine and its metabolites and whether morphine clearance is related to treatment outcome.

methodsBlood samples from 49 cancer patients treated with oral and/or subcutaneous morphine were prospectively collected and were used to develop a population pharmacokinetic model for morphine, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). The influence of age, gender, renal function and several polymorphisms possibly related to the pharmacokinetics of the three compounds was investigated. In addition, the relation between treatment failure and morphine and metabolite clearances was explored.

resultsA one-compartment model including an extensive first-pass effect adequately described the data of morphine and its metabolites. Estimated mean area under the plasma concentration-time curve (AUC) ratios following oral versus subcutaneous administration were: M3G/morphine 29.7:1 vs. 11.1:1; M6G/morphine 5.26:1 vs. 1.95:1; and M3G/M6G 5.65:1 vs. 5.70:1. Renal function was significantly correlated with clearance of the metabolites, which increased 0.602 L/h per every 10 mL/min/1.73 m

conclusionThe influence of age-, gender- and pharmacokinetic-related polymorphisms was not identified on the pharmacokinetics of morphine. Clearance of morphine or its metabolites was not found to explain treatment outcome; however, large variations in plasma concentrations of morphine, M3G and M6G support further studies on the relation between plasma concentrations and treatment outcome. Dutch Trial Register ID: NTR4369.

Indexed as

Models, BiologicalAdministration, OralAdultAgedAged, 80 and overAnalgesics, OpioidATP-Binding Cassette, Sub-Family C ProteinsFemaleGlucuronosyltransferaseHumansInfusions, SubcutaneousMaleMiddle AgedMorphineMorphine DerivativesNeoplasmsAnalgesics, OpioidATP-Binding Cassette, Sub-Family C ProteinsGlucuronosyltransferaseMorphinemorphine-3-glucuronidemorphine-6-glucuronideMorphine Derivativesmultidrug resistance-associated protein 3Organic Cation Transporter 1UGT2B7 protein, human

Identifiers

PMID27815868
PMCPMC5488155
OpenAlexW2548301349

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Registered trials

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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.