Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects
Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK...
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| Format: | Article |
| Language: | English |
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Wiley
2018-01-01
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| Series: | Pain Research and Management |
| Online Access: | http://dx.doi.org/10.1155/2018/7276021 |
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| author | Lynn R. Webster Carmela Pantaleon Matthew Iverson Michael D. Smith Eric R. Kinzler Stefan Aigner |
| author_facet | Lynn R. Webster Carmela Pantaleon Matthew Iverson Michael D. Smith Eric R. Kinzler Stefan Aigner |
| author_sort | Lynn R. Webster |
| collection | DOAJ |
| description | Objective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine. |
| format | Article |
| id | doaj-art-91ee9652c6364d84bc04ae6f56c463fb |
| institution | Kabale University |
| issn | 1203-6765 1918-1523 |
| language | English |
| publishDate | 2018-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pain Research and Management |
| spelling | doaj-art-91ee9652c6364d84bc04ae6f56c463fb2025-02-03T05:58:26ZengWileyPain Research and Management1203-67651918-15232018-01-01201810.1155/2018/72760217276021Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced SubjectsLynn R. Webster0Carmela Pantaleon1Matthew Iverson2Michael D. Smith3Eric R. Kinzler4Stefan Aigner5PRA Health Sciences, Salt Lake City, UT, USAInspirion Delivery Sciences LLC, Morristown, NJ, USAInspirion Delivery Sciences LLC, Morristown, NJ, USAPRA Health Sciences, Salt Lake City, UT, USAInspirion Delivery Sciences LLC, Morristown, NJ, USAInspirion Delivery Sciences LLC, Morristown, NJ, USAObjective. To investigate the pharmacokinetics (PK) of Morphine ARER, an extended-release (ER), abuse-deterrent formulation of morphine sulfate after oral and intranasal administration. Methods. This randomized, double-blind, double-dummy, placebo-controlled, four-way crossover study assessed the PK of morphine and its active metabolite, M6G, from crushed intranasal Morphine ARER and intact oral Morphine ARER compared with crushed intranasal ER morphine following administration to nondependent, recreational opioid users. The correlation between morphine PK and the pharmacodynamic parameter of drug liking, a measure of abuse potential, was also evaluated. Results. Mean maximum observed plasma concentration (Cmax) for morphine was lower with crushed intranasal Morphine ARER (26.2 ng/mL) and intact oral Morphine ARER (18.6 ng/mL), compared with crushed intranasal ER morphine (49.5 ng/mL). The time to Cmax (Tmax) was the same for intact oral and crushed intranasal Morphine ARER (1.6 hours) and longer for crushed intranasal morphine ER (1.1 hours). Higher mean maximum morphine Cmax, Tmax, and abuse quotient (Cmax/Tmax) were positively correlated with maximum effect for drug liking (R2 ≥ 0.9795). Conclusion. These data suggest that Morphine ARER maintains its ER profile despite physical manipulation and intranasal administration, which may be predictive of a lower intranasal abuse potential compared with ER morphine.http://dx.doi.org/10.1155/2018/7276021 |
| spellingShingle | Lynn R. Webster Carmela Pantaleon Matthew Iverson Michael D. Smith Eric R. Kinzler Stefan Aigner Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects Pain Research and Management |
| title | Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects |
| title_full | Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects |
| title_fullStr | Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects |
| title_full_unstemmed | Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects |
| title_short | Intranasal Pharmacokinetics of Morphine ARER, a Novel Abuse-Deterrent Formulation: Results from a Randomized, Double-Blind, Four-Way Crossover Study in Nondependent, Opioid-Experienced Subjects |
| title_sort | intranasal pharmacokinetics of morphine arer a novel abuse deterrent formulation results from a randomized double blind four way crossover study in nondependent opioid experienced subjects |
| url | http://dx.doi.org/10.1155/2018/7276021 |
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