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23rd Annual Meeting
February 7-10, 2007
New Orleans, LA
© 2006 American Academy of Pain Medicine
 


Thursday, February 8, 2007
148

Effect Of Alcohol Ingestion On The In Vivo Pharmacokinetics Of KADIAN®

Franklin Johnson, MS, Alpharma Branded Products Division Inc., Piscataway, NJ, USA, Stephen Sun, MD, Alpharma Branded Products Division Inc., Piscataway, NJ, USA, Joseph Stauffer, DO, Alpharma Branded Products Division Inc., Piscataway, NJ, USA, and George Wagner, Alpharma Branded Products Division Inc., Piscataway, NJ, USA.

INTRODUCTION

When hydromorphone hydrochloride extended-release capsules (PalladoneTM) were removed from the market in 2005 due to pharmacokinetic data indicating co-ingestion with alcohol results in dangerous increases in peak plasma hydromorphone concentrations,1 there was a call to study in vivo interactions of other extended-release products with alcohol. This study assessed the single-dose relative bioavailability of KADIAN® (morphine sulfate extended-release) Capsules taken with alcohol.

METHODS

This was an IRB-approved, open-label, randomized, single-dose, 3-way crossover study in 32 opioid-naïve, healthy male volunteers, aged 21-40 years, who were moderate drinkers (7-21 drinks/week) recruited through MDS Pharma Services. Subjects took a 100mg KADIAN® capsule along with 240mL of 40% alcohol (4 shots [101mL] 190-proof Everclear®, 139mL water) fasted and fed, and with 240mL of water (fasted) as a reference. An open-label arm of immediate-release 20mg morphine solution was included for comparison. Oral naltrexone hydrochloride was administered 12h and 2h prior to treatment to counter morphine effects.

RESULTS

Twenty-seven subjects had evaluable pharmacokinetic data for ≥1 treatment arm. Eleven subjects vomited after taking KADIAN®+alcohol; none vomited after taking KADIAN®+water. Overall, median Tmax was 6.0, 8.0, and 8.0h, respectively. Excluding patients who vomited during the 12h dosing interval (FDA Guidance on Oral Bioavailability/Bioequivalence studies2), mean of log-transformed Cmax values for subjects taking KADIAN®+alcohol fasted (n=15) and fed (n=21) were 16.7 and 16.0ng/mL, similar to the Cmax of 15.6ng/mL in subjects consuming KADIAN®+water (n=21). ANOVA showed ratios of least square means for Cmax and AUC of both regimens of KADIAN®+alcohol within 80%-125% confidence interval boundaries when compared with KADIAN®+water. Pharmacokinetic profile of 20mg solution was markedly different from the test treatments.

CONCLUSIONS

KADIAN® taken with 240mL of 40% alcohol continued to display extended-release characteristics. Visual inspection of concentration-time profiles showed only a modest effect on release characteristics of extended-release morphine.


References: 1. Food and Drug Administration. Alert for Healthcare Professionals: Hydromorphone Hydrochloride Extended-Release Capsules (marketed as Palladone). July 2005. Available at: www.fda.gov/cder/drug/InfoSheets/HCP/hydromorphoneHCP.htm. Accessed September 28, 2006.

2. Food and Drug Administration. Guidance for Industry: Bioavailability and Bioequivalence Studies for Orally Administered Drug Products—General Considerations. Rockville, Md: Center for Drug Evaluation and Research; March 2003.
Funding: funding was provided by Alpharma Branded Products Division, Inc.

Stephen Sun, MD
Conflict of Interest Disclosure: Alpharma Branded Products Division Inc., employee

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