A bioequivalence study of oral controlled-release morphine using naltrexone blockade

Area of Science:

• Pharmacokinetics and Drug Bioavailability
• Clinical Pharmacology
• Opioid Analgesics

Background:

• Morphine sulfate (MS Contin) is a controlled-release formulation for pain management.
• Assessing the bioavailability of different dosage forms is crucial for therapeutic equivalence.
• Naltrexone is an opioid antagonist used to block the effects of opioids.

Purpose of the Study:

• To compare the bioavailability of a single 200-mg oral controlled-release morphine sulfate (MSC) tablet versus two 100-mg MSC tablets.
• To evaluate the efficacy of naltrexone in blocking the pharmacological effects of controlled-release morphine.
• To establish bioequivalence between the 200-mg and 100-mg MSC dosage forms.

Main Methods:

• Randomized, analytically blinded, two-way crossover study in 23 normal volunteers.
• Administration of three doses of naltrexone (100 mg each) to block morphine effects.
• Comparison of pharmacokinetic parameters (Cmax, AUC0-24) between one 200-mg MSC tablet and two 100-mg MSC tablets.

Main Results:

• The 200-mg MSC tablet demonstrated 96% bioavailability compared to two 100-mg tablets (90% CI: 88.14-105.74%).
• Pharmacokinetic parameters (Cmax, AUC0-24) for the 200-mg tablet were within +/- 20% of the two 100-mg tablets, confirming bioequivalence.
• Naltrexone effectively blocked morphine's effects, and the 200-mg MSC dose with naltrexone was well-tolerated.

Conclusions:

• The single 200-mg oral controlled-release morphine sulfate tablet is bioequivalent to two 100-mg MSC tablets.
• Naltrexone is safe and effective for blocking controlled-release morphine effects in bioavailability studies.
• This study supports the use of naltrexone in evaluating high-dose morphine formulations in healthy volunteers.