Preclinical study of an oral controlled release naltrexone complex in mice

• Published in: Journal of pharmacy and pharmacology Vol. 52; no. 6; p. 659
• Main Authors: Alvarez-Fuentes, J, Rojas-Corrales, M O, Holgado, M A, Caraballo, I, Micó, J A, Fernández-Arévalo, M
• Format: Journal Article
• Language: English
• Published: England 01.06.2000
• Subjects: Administration, Oral; Animals; Delayed-Action Preparations; Drug Administration Schedule; Male; Mice; Naltrexone - administration & dosage; Naltrexone - pharmacokinetics; Narcotic Antagonists - administration & dosage; Narcotic Antagonists - pharmacokinetics; Substance-Related Disorders - drug therapy
• ISSN: 0022-3573
• DOI: 10.1211/0022357001774499

Naltrexone, a long-acting, orally effective, opioid antagonist which blocks opioid effects as well as the development of physical dependence, would appear to be a drug ideally suited to addiction treatment. An optimal dosage regimen is critical for the treatment patient compliance in ambulatory opiate detoxification programs. The ideal dosage regimen would be an oral controlled-release system of naltrexone that allowed once-a-day administration providing stable plasma levels. A naltrexone-Eudragit L complex was produced in aqueous medium from naltrexone hydrochloride solution and Eudragit L30D (30% w/v) previously diluted (6% w/v) and partially neutralized. The antagonistic activity of naltrexone-Eudragit L on morphine-induced thermal antinociception, in comparison with conventional naltrexone, was evaluated, using the mouse hot-plate model. Mice were administered 10 mg kg(-1) morphine subcutaneously, 10 min before test, and the antagonist products, either naltrexone-Eudragit L or naltrexone hydrochloride, were administered orally at 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16h before the test. The results showed that the antagonism induced by naltrexone-Eudragit L was effective until 12 h after drug administration, while that induced by naltrexone hydrochloride disappeared 10 h after its administration. A 23.47% increase of the area under curve was obtained when naltrexone-Eudragit L was administered, compared with that induced by conventional naltrexone. The time taken to decrease the inhibition of analgesic activity to 50% was delayed by 51.80%. This complexation technique can be considered as a useful tool in the design of oral controlled-release systems capable of inducing a long-lasting effect in-vivo.