Effects of ethanol on the pharmacokinetics of extended-release oxycodone with sequestered naltrexone (ALO-02).
ALO-02 capsules, intended to deter abuse, contain pellets of extended-release oxycodone hydrochloride (HCl), an opioid agonist, surrounding sequestered naltrexone HCl, an opioid antagonist. The objective of this study was to determine the effects of administration of ALO-02 with 20 or 40 % ethanol on the pharmacokinetics of oxycodone.



This was an open-label, single-dose, randomized, three-way crossover study in 18 healthy fasting adults administered ALO-02 20/2.4 mg (oxycodone/naltrexone) with water, 20 % ethanol, or 40 % ethanol, each under naltrexone block.



Median time to maximum concentration was 12 h postdose when ALO-02 was administered with water or 20 % ethanol and decreased to 8 h postdose with 40 % ethanol. Geometric mean area under the plasma concentration-time curve (AUC) from time zero extrapolated to infinity (AUC∞) and maximum concentration (Cmax) values were similar for ALO-02 administered with water or 20 % ethanol, and increased by about 13 and 37 %, respectively, for ALO-02 administered with 40 % ethanol versus water. The 90 % confidence intervals (CIs) for AUC∞ and Cmax ratios of ALO-02 with 20 % ethanol versus water were within 80-125 %; upper 90 % CIs were >125 % for ALO-02 with 40 % ethanol versus water. The most common adverse events were mild-to-moderate vomiting, nausea, headache, and somnolence. Incidence of adverse events increased for ALO-02 given with ethanol versus water.



Oxycodone exposures (Cmax) were unaffected when ALO-02 was administered with 20 % ethanol but Cmax increased by 37 % with 40 % ethanol versus water. ALO-02 administered with ethanol under naltrexone block was generally well tolerated.
Clinical Pharmacology, Pfizer Inc, 235 East 42nd Street, New York, NY, 10017, USA, bimal.k.malhotra@pfizer.com.
Bimal K
BK
Malhotra
Kyle
K
Matschke
Qiang
Q
Wang
Candace
C
Bramson
Joanne
J
Salageanu
D000328:Adult; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D010098:Oxycodone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D009292:Narcotic Antagonists; C000608978:oxycodone naltrexone combination; D000431:Ethanol; D009271:Naltrexone; D010098:Oxycodone