Assessment of Pharmacodynamic Effects Following Oral Administration of Crushed Morphine Sulfate and Naltrexone Hydrochloride Extended-Release Capsules Compared with Crushed Morphine Sulfate Controlled-Release Tablets and Placebo in Nondependent Recreational Opioid Users

Setnik, Beatrice; Sommerville, Kenneth W.; Goli, Veeraindar; Han, Ling; Webster, Lynn R.

doi:10.1111/pme.12148

Cited by 23 publications

(10 citation statements)

References 22 publications

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“…The morphineinduced miosis observed in the present study is in good agreement with previous studies of opioid-induced miosis e.g. (Lotsch et al, 2002;Matouskova et al, 2011;Setnik et al, 2013). The effect was present 30 min after morphine administration, which corresponds well with the expected and measured onset of analgesia.…”

Section: Assessment Of Subjective and Objective Measuressupporting

confidence: 92%

“…Several such measures are available, however no previous studies have assessed them in combination and it is not yet known which is the most sensitive to monitor the effects of opioids. Following a sufficient dose of an opioid drug, pupillary miosis is induced and pupil diameter has therefore been a frequently used objective index of CNS effects of opioids in humans (Macleod et al, 2012;Matouskova, Slanar, Chytil, & Perlik, 2011;Setnik, Sommerville, Goli, Han, & Webster, 2013;Skarke, Darimont, Schmidt, Geisslinger, & Lotsch, 2003;Slanar, Nobilis, Kvetina, Idle, & Perlik, 2006;Stoops, Glaser, & Rush, 2013;Weinhold & Bigelow, 1993). Thus, one objective approach is to use pupillometry.…”

Section: Introductionmentioning

confidence: 99%

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Objective markers of the analgesic response to morphine in experimental pain research

Brokjær

Olesen

Kreilgaard

et al. 2015

Journal of Pharmacological and Toxicological Methods

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Section: Assessment Of Subjective and Objective Measuressupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Objective markers of the analgesic response to morphine in experimental pain research

Brokjær

Olesen

Kreilgaard

et al. 2015

Journal of Pharmacological and Toxicological Methods

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“…E max at-the-moment Drug Liking VAS scores for naltrexone were similar to placebo (median difference, 0.0) ( Figure 3). In addition, oxycodone and pentazocine demonstrated significantly higher E max at-the-moment Drug Liking VAS scores than samidorphan [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24].5], respectively; P < .001), with differences exceeding the prespecified 7-point margin for these comparisons (Figure 3).…”

Section: Pharmacodynamicsmentioning

confidence: 99%

Abuse Potential of Samidorphan: A Phase I, Oxycodone‐, Pentazocine‐, Naltrexone‐, and Placebo‐Controlled Study

Pathak

Vince

Kelsh

et al. 2018

The Journal of Clinical Pharma

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Samidorphan is a μ-opioid receptor antagonist in development for the treatment of schizophrenia,in combination with olanzapine,and major depressive disorder, in combination with buprenorphine, at proposed therapeutic doses of samidorphan 10 mg and 2 mg, respectively. A double-blind, doubledummy, active-and placebo-controlled, crossover study evaluated the abuse potential of samidorphan in healthy, nondependent, recreational opioid users. Following a qualification phase, participants were randomized to 1 of 6 treatment sequences of study drugs: placebo, samidorphan (10 or 30 mg), oxycodone (40 mg), pentazocine (30 mg), and naltrexone (100 mg) in a 6 × 6 Williams design. The primary end point was maximum effect (E max ) for "at-the-moment" Drug Liking visual analog scale scores. Secondary end points included E max visual analog scale scores for Take Drug Again and Overall Drug Liking and safety assessments. Among 47 participants, at-the-moment E max Drug Liking scores for positive study controls oxycodone and pentazocine were significantly higher than placebo (P < .001) and samidorphan (both doses; P < .001). Both samidorphan doses had E max Drug Liking scores similar to placebo and naltrexone (median within-subject differences of 0.0). E max Take Drug Again scores for samidorphan (both doses) were higher than placebo, but similar to naltrexone, an unscheduled μ-opioid receptor antagonist. Adverse events to evaluate abuse potential occurred less frequently with samidorphan, naltrexone, and placebo than with oxycodone and pentazocine. Findings from this study support a lack of abuse potential with samidorphan at doses up to 30 mg and a safety profile consistent with previous samidorphan clinical studies.

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“…In adults, pupillometry has been studied as a method to quantitate pain11 and to assess opioid pharmacodynamics 12 13. The extent of pupil dilatation can provide an index of nociceptive input via autonomic innervation of the iris muscles,14 15 while the extent of attenuation in this pupillary response during exposure to opioid analgesics can provide an index of pharmacological effect by reflecting the extent of occupancy of μ and κ opioid receptors in the central nervous system 16.…”

Section: Introductionmentioning

confidence: 99%

Pupillometry: a non-invasive technique for pain assessment in paediatric patients

Connelly

Brown

Kearns

et al. 2014

Archives of Disease in Childhood

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Objective Pupillometry has been used to assess both pain intensity and response to analgesic medications in adults. The aim of this observational study was to explore proof-of-concept for the use of this technique in paediatric patients. Changes in pupil parameters before and after opioid exposure also were evaluated. Design and Setting This was a single-center, prospective study conducted at an academic paediatric medical center. Patients Children 9-17 years of age undergoing elective surgical correction of pectusexcavatum were enrolled into a protocol approved by the human ethical committee (IRB). Interventions Pupil size and reactivity were measured using a hand-held pupillometer. Pain was assessed using age-appropriate, validated pain self-report scales. Results Thirty patients were enrolled. Each point change on a 10 cm visual analog pain intensity scale was associated with a statistically significant mean change of 0.11 mm/s in maximum pupil constriction velocity, and of approximately 0.4% in pupil diameter. As expected, there was an association between total opioid dose (expressed as morphine equivalents) and pupil diameter. Age, sex, and baseline anxiety scores did not correlate significantly with pupillary response. Conclusion The association of both maximum pupillary constriction velocity and diameter with pain scores illustrates the potential for using pupillometry as a non-invasive method to objectively quantitate pain response/intensity in children. The technique holds promise as a pharmacodynamic “tool” to assess opioid response in paediatric patients.

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Assessment of Pharmacodynamic Effects Following Oral Administration of Crushed Morphine Sulfate and Naltrexone Hydrochloride Extended-Release Capsules Compared with Crushed Morphine Sulfate Controlled-Release Tablets and Placebo in Nondependent Recreational Opioid Users

Cited by 23 publications

References 22 publications

Objective markers of the analgesic response to morphine in experimental pain research

Objective markers of the analgesic response to morphine in experimental pain research

Abuse Potential of Samidorphan: A Phase I, Oxycodone‐, Pentazocine‐, Naltrexone‐, and Placebo‐Controlled Study

Pupillometry: a non-invasive technique for pain assessment in paediatric patients

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