AI Article Synopsis
- This study examines benzhydrocodone, a prodrug of hydrocodone, to evaluate its pharmacokinetics and potential for abuse compared to hydrocodone bitartrate (HB).
- Participants were healthy, nondependent adults who received intranasal doses of both drugs and reported their experiences.
- Results showed lower hydrocodone levels and reduced drug liking with benzhydrocodone, indicating it may have a lower potential for abuse than traditional hydrocodone products.
Article 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.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6294406 | PMC |
| http://dx.doi.org/10.1093/pm/pnx247 | DOI Listing |
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