Abstract |
Pharmacotherapy treatment for alcoholism is limited by poor compliance, adverse effects, and fluctuating drug levels after bolus administration. A long-term delivery system would improve upon these limitations. The current study describes the characterization of a sustained release implant containing nalmefene, an opioid antagonist, for treatment of alcoholism. Nalmefene was blended with ethylene vinyl acetate (EVA), extruded into 2.8 mm x 27 mm rods, and coated with EVA to optimize release. In vitro release was determined by HPLC, and in vivo release characteristics after subcutaneous implantation into rats were determined by LC-MS/MS analyses. Extrusion produced rods containing 80.09 +/- 6.0 mg nalmefene. In vitro release was high from the uncoated rods, and they were depleted of drug fairly quickly; however EVA coatings maintained release over longer periods. The 25 wt.% coated rods provided in vitro release of 0.36 mg/day/rod, and in vivo release of 0.29 mg/day/rod over 6 months, and showed dose-dependent nalmefene plasma concentrations (one rod: 3.33 +/- 0.56 ng/ml, three rods: 10.19 +/- 2.31 ng/ml). After explantation, nalmefene plasma concentrations were undetectable by 6 h. A sustained release nalmefene rod provides 6 months of drug with no adverse effects.
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Authors | Lauren C Costantini, Sofie R Kleppner, Joseph McDonough, Marc R Azar, Raj Patel |
Journal | International journal of pharmaceutics
(Int J Pharm)
Vol. 283
Issue 1-2
Pg. 35-44
(Sep 28 2004)
ISSN: 0378-5173 [Print] Netherlands |
PMID | 15363499
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Delayed-Action Preparations
- Narcotic Antagonists
- Naltrexone
- nalmefene
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Topics |
- Alcoholism
(drug therapy)
- Animals
- Area Under Curve
- Delayed-Action Preparations
- Equipment Design
- Humans
- Infusion Pumps, Implantable
- Male
- Naltrexone
(administration & dosage, analogs & derivatives, pharmacokinetics, therapeutic use)
- Narcotic Antagonists
(administration & dosage, pharmacokinetics, therapeutic use)
- Rats
- Rats, Wistar
- Technology, Pharmaceutical
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