Remoxy In Vivo Abuse Resistance Studies

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RemoxyIn Vivo Abuse Resistance Studies

• Ping Ji, PhD
• Senior Clinical Pharmacologist
• Office of Clinical Pharmacology
• Center of Drug Evaluation and Research
• Food and Drug Administration

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In Vivo Abuse Resistance Studies

• Physical Disruption Study
• Mastication (chewing) Study
• Buccal Absorption Study

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Dose Dumping

• For opioids, Cmax is a critical pharmacokinetic
  parameter
• For the assessment of dose dumping, it is
  important to examine data from both individual
  and group mean basis

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Cumulative Frequency Analysis

• In a data set, the more than cumulative
  frequency of a value x is the total number of
  observations that are more than or equal to x
• Frequency counts can be measured in terms of
  absolute numbers or relative numbers (e.g.,
  proportions or percentages)

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Physical Disruption Study

• Treatment A Remoxy 40 mg capsule (whole)
• Treatment B Remoxy 40 mg capsule (crushed,
  extracted with solvent)
• Treatment C OxyContin 40 mg tablet (whole)
• Treatment D OxyContin 40 mg tablet (crushed,
  extracted with solvent)
• Treatment E Oxycodone oral solution 40 mg

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Physical Disruption Study
Mean Oxycodone Plasma Concentration-Time Profiles
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Physical Disruption Study
Mean Oxycodone Plasma Concentration-Time Profiles
OxyContin
Remoxy
Statistical Comparison
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Physical Disruption Study
Mean Oxycodone Plasma Concentration-Time Profiles
Statistical Comparison
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Physical Disruption Study
Cumulative Frequency Plots
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Physical Disruption Study Conclusion

• The extended-release characteristics appeared to
  be compromised when Remoxy was subjected crushing
  and extraction with a solvent

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Mastication Study

• Treatment A Remoxy 40 mg capsule (whole)
• Treatment B Remoxy 40 mg capsule masticated
  rigorously and then swallowed
• Treatment C Oxycondone oral solution 40 mg

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Mastication Study
Mean Oxycodone Plasma Concentration-Time Profiles
Statistical Comparison
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Mastication Study
Cumulative Frequency Plots
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Mastication Study Conclusion

• The extended-release characteristics appeared to
  be compromised when Remoxy was subjected to
  mastication

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Buccal Absorption Study

• Treatment A Remoxy 40 mg capsule (whole)
• Treatment B Remoxy 40 mg capsule held in the
  buccal cavity and then swallowed
• Treatment C Oxycodone oral solution 40 mg

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Buccal Absorption Study
Mean Oxycodone Plasma Concentration-Time Profiles
Statistical Comparison
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Buccal Absorption Study
Cumulative Frequency Plots
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Buccal Absorption Study Conclusion

• The extended-release characteristics appeared to
  be compromised when Remoxy was subjected to
  buccal absorption

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Overall Summary

• The extended-release characteristics appeared to
  be compromised when Remoxy was subjected to
  crushing and extraction with ethanol,
  mastication, and buccal absorption