The objective of this study was to compare the single-dose relative bioavailability of
Alpharma Branded Products Division Inc. (KADIAN) 100 mg morphine sulfate extended-release
capsules when dosed with alcohol under fasting and fed conditions compared to water.
In addition, the pharmacokinetics of an immediate release solution following a 20 mg dose
was assessed for informational purposes and for possible modeling.
Minimum age: 21 Years.
Maximum age: 40 Years.
Gender(s): Male.
Inclusion Criteria:
- Healthy adult male volunteers, 21 to 40 years of age.
- Subjects were non-smokers for at least 3 months or light smokers (less than 10
pack-years).
- Subjects with a history of moderate consumption of at least 7-21 units of alcohol per
week or the alcohol equivalent (12 oz beer = 5 oz of 80-proof distilled spirits = 1
unit).
- Weighing at least 70 kg and within 20% of their ideal weights (table of "Desirable
Weights of Adults", Metropolitan Life Insurance Company, 1983).
- Medically healthy subjects with no clinically significant abnormalities in their
laboratory profile and ECGs, as deemed by the Principal Investigator.
- Voluntarily consented to participate in the study.
Exclusion Criteria:
- History or presence of significant cardiovascular, pulmonary, hepatic, renal,
hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, or
psychiatric disease.
- In addition, history or presence of: alcoholism or drug abuse; asthma or other
chronic respiratory illness; diabetes; gastrointestinal dysmotility, irritable bowel
syndrome, chronic constipation or recent enteritis; hypersensitivity or idiosyncratic
reaction to morphine or other opioids; hypersensitivity or idiosyncratic reaction to
naltrexone, naloxone, or other opioids antagonists.
- History of no alcohol intake (alcohol-naive) or less than moderate alcohol intake.
- Subject with a history of alcohol intake exceeding the equivalence of 21 units/week
or exceeding the average of 3 drinks per day.
- Subjects who had a surgery of the gastrointestinal tract (except appendectomy) which
would interfere with absorption of the study drug.
- Subjects who received hepatic enzyme inducing drugs (e. g. Nizoral, Tagamet) within
the previous three months.
- Subjects whose QTc interval was >450 msec at screening and prior to dosing.
- Subjects whose sitting blood pressure was less than 110/45 mm Hg at screening or
100/45 mm Hg before dosing.
- Subjects who had been on a special diet (for whatever reason) during the 28 days
prior to the first dose and throughout the study.
- Subjects who had made any significant donation or loss of blood within 56 days.
- Subjects who had made a plasma donation within 7 days prior to the study.
- Subjects with hemoglobin less than 12. 0 g/dL.
- Subjects who had participated in another clinical trial within 28 days prior to the
first dose.
- Subjects who had a positive urine test for drugs of abuse or alcohol.
- Subjects who had a positive test for, or had been treated for hepatitis B, hepatitis
C or HIV.