Evidence map›Paper›PMID 29092079›Full record

Trial reportPain medicine (Malden, Mass.)2018

Pharmacokinetics and Abuse Potential of Benzhydrocodone, a Novel Prodrug of Hydrocodone, After Intranasal Administration in Recreational Drug Users.

Travis C Mickle, Sven M Guenther, Andrew C Barrett, Kathryn Ann Roupe, Jing Zhou, Daniel Dickerson, Lynn R Webster

Open access · hybridAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Pain medicine (Malden, Mass.), 2018. 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
0.5field-weighted citation impact, top 25% 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, 7 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. 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

7 authors at 3 institutions in 1 country.

Travis C MickleKemPharm, Coralville, Iowa.
Sven M GuentherKemPharm, Coralville, Iowa.
Andrew C BarrettKemPharm, Coralville, Iowa.
Kathryn Ann RoupeWorldwide Clinical Trials, Austin, Texas.
Jing ZhouWorldwide Clinical Trials, Austin, Texas.
Daniel DickersonPRA Health Sciences, Lenexa, Kansas, USA.
Lynn R WebsterPRA Health Sciences, Lenexa, Kansas, USA.
KemPharm (United States) · USPRA Health Sciences · USWorldwide Clinical Trials (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Objective: Developing an acetaminophen-free, immediate-release hydrocodone product remains an unmet medical need; however, new opioid analgesics should not introduce new abuse risks. Benzhydrocodone is a prodrug of hydrocodone that must be metabolized into hydrocodone by enzymes in the intestinal tract to optimally deliver its pharmacologic effects. This study evaluated the intranasal pharmacokinetics and abuse potential of benzhydrocodone active pharmaceutical ingredient (API) compared with hydrocodone bitartrate (HB) API. Design: Single-center, randomized, double-blind, crossover study. Setting: Clinical research site. Subjects: Healthy adult, nondependent, recreational opioid users. Methods: Subjects (N = 51 Completers) were randomized to receive 13.34 mg of intranasal benzhydrocodone API and 15.0 mg of intranasal HB API (molar-equivalent doses of hydrocodone). Blood samples were taken, and Drug Liking scores (assessed on a bipolar visual analog scale) were obtained throughout each dosing interval. Nasal irritation and safety were assessed. Results: Peak hydrocodone plasma concentration (Cmax) was 36.0% lower, and total hydrocodone exposures (AUClast and AUCinf) were 20.3% and 19.5% lower, respectively, for benzhydrocodone API compared with HB API (P < 0.0001). All partial AUC values were lower for benzhydrocodone API, with a ≥ 75% reduction in hydrocodone exposure at all time intervals up to one hour postdose (P < 0.0001). Median Tmax of hydrocodone following benzhydrocodone API was delayed by more than one hour compared with HB. Drug Liking score, as assessed by maximal liking (Emax), was significantly lower for benzhydrocodone API vs HB API (P = 0.004), with 45% of subjects showing a ≥ 30% reduction in Drug Liking Emax. Conclusion: Reductions in hydrocodone exposure and associated decreases in Drug Liking relative to HB suggest that the prodrug benzhydrocodone may deter intranasal abuse.

Indexed as

AcetaminophenAdministration, IntranasalAdultAnalgesics, OpioidCross-Over StudiesDouble-Blind MethodDrug CombinationsFemaleHumansHydrocodoneMaleMiddle AgedOpioid-Related DisordersYoung AdultAcetaminophenacetaminophen, hydrocodone drug combinationAnalgesics, OpioidDrug CombinationsHydrocodone

Identifiers

PMID29092079
PMCPMC6294406
OpenAlexW4251234672

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.