Evidence map›Paper›PMID 25121773›Full record

Trial reportPloS one2014

Effects of aprepitant on the pharmacokinetics of controlled-release oral oxycodone in cancer patients.

Yutaka Fujiwara, Masanori Toyoda, Naoko Chayahara, Naomi Kiyota, Takanobu Shimada, Yoshinori Imamura, Toru Mukohara, Hironobu Minami

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
1.1field-weighted citation impact, top 22% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Aprepitant and fosaprepitant drug interactions: a systematic review.British journal of clinical pharmacology · 2017
    Pooled it
  2. Hydrocodone, Oxycodone, and Morphine Metabolism and Drug-Drug Interactions.The Journal of pharmacology and experimental therapeutics · 2023
    Review
  3. Article
  4. Article
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 1 institution in 1 country.

Yutaka FujiwaraDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Investigational Cancer Therapeutics, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center Hospital, Chiba, Japan.
Masanori ToyodaDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Naoko ChayaharaDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Naomi KiyotaDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Takanobu ShimadaDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Yoshinori ImamuraDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan.
Toru MukoharaDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan; Cancer Center, Kobe University Graduate School of Medicine, Kobe, Japan.
Hironobu MinamiDivision of Medical Oncology/Hematology, Kobe University Graduate School of Medicine, Kobe, Japan; Cancer Center, Kobe University Graduate School of Medicine, Kobe, Japan.
Kobe University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeOxycodone is a µ-opioid receptor agonist widely used in the treatment of cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a minor proportion undergoes 3-O-demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release (CR) oxycodone.

methodThis study design was an open-label, single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours. Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning). The steady-state trough concentrations (Css) were measured from day 1 to day 3.

resultsAprepitant increased the area under the plasma concentration-time curve (AUC0-8) of oxycodone by 25% (p<0.001) and of oxymorphone by 34% (p<0.001), as well as decreased the AUC0-8 of noroxycodone by 14% (p<0.001). Moreover, aprepitant increased Css of oxycodone by 57% (p = 0.001) and of oxymorphone by 36% (p<0.001) and decreased Css of noroxycodone by 24% (p = 0.02) at day 3 compared to day 1.

conclusionsThe clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose.

trial registrationUMIN.ac.jp UMIN000003580.

Indexed as

AdultAgedAnalgesics, OpioidAprepitantArea Under CurveDelayed-Action PreparationsFemaleHumansMaleMiddle AgedMorphinansMorpholinesNeoplasmsOxycodoneOxymorphonePainAnalgesics, OpioidAprepitantDelayed-Action PreparationsMorphinansMorpholinesnoroxycodoneOxycodoneOxymorphone

Identifiers

PMID25121773
PMCPMC4133207
OpenAlexW2123359903

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.