Effectiveness of repeated administration of a new oral naltrexone controlled-release system on morphine analgesia.
Naltrexone hydrochloride, an opioid antagonist used as an adjunct to the maintenance of the opioid-free state for detoxified individuals, was introduced into the polymeric structure of Eudragit L30D, an anionic copolymer based on polymethacrylic acid and ethylacrylate. From the results of a preclinical study, this complexation technique can be considered as a useful tool in the design of oral controlled-release systems (naltrexone-Eudragit L) capable of inducing long-lasting effects in-vivo. The biopharmaceutical characterization of the naltrexone-Eudragit L complex in comparison with naltrexone hydrochloride using the mouse hot-plate model has been previously carried out. The results showed a longer effect, an enhancement of 23.47% of the area under the curve of the inhibition of analgesic activity vs time, and a delay of 51.80% in the t1/2 value induced by the complex, compared with those induced by conventional naltrexone. In this study, a regimen of chronic administration of naltrexone-Eudragit L was established. Thus, in an 8-day treatment (4 doses in alternate days) this oral controlled-release system effectively antagonized the analgesic effect of morphine for 8 h, whereas naltrexone hydrochloride has to be administered over 16 days (8 doses in alternate days) to induce the same effect. In the 16-day schedule the complex-induced antagonism lasted over 14 h after administration.
Alvarez-Fuentes
J
J
Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, University of Seville, Spain. arevalo@fafar.us.es
Rojas -Corrales
M O
MO
Holgado
M A
MA
Sánchez-Lafuente
C
C
Micó
J A
JA
Fernández -Arévalo
M
M
D000284:Administration, Oral; D000818:Animals; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage* / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D010146:Pain
D003692:Delayed-Action Preparations; D009292:Narcotic Antagonists; D009294:Narcotics; D009271:Naltrexone; D009020:Morphine