An improved long-acting delivery system for narcotic antagonists.

摘要: The feasibility of using cholesterol-glyceryltristearate matrix for prolonged release naltrexone was evaluated in rats. Implantable cylindrical pellets (cholesterol 105 mg, glyceryl tristearate 15 mg and 30 mg), diameter 4.5 mm, length 9 blocked the antinociceptive action (hot plate 55 degrees C) 10 mg/kg s.c. challenge dose morphine rats 3 months. rate from or 50 approximated first-order kinetics with t1/2 alpha 20-26 days beta 40-60 days. factors affecting drug delivery system were ratio cholesterol to naltrexone, loading level surface area unit volume dosage form. minimum block effect about 4 5 microgram/kg/hr. cumulative urinary excretion radioactivity [3H] implanted after 30, 60, 90 17.7, 23.7, 25.7% respectively percent released at these times 55.8, 68.8, 78.2 respectively. devices possess desirable characteristics simplicity, nontoxicity, nonirritability, ease sterilization ethylene oxide, small size easy insertion removal, absence encapsulation by surrounding tissue, an extended period unaffected body metabolism. Neither deterioration implant nor gross anatomic histological changes site occurred 6 months 1 year implantation aside some enhanced sexual activity (e.g., spontaneous penile erections) no side effects observed rats, which fed well gained weight during entire treatment. concentrations free brains pellet-implanted significantly lower (24 15%) as compared placebo controls 0.5 1.0 hr a [6-3H] morphine. We are currently evaluating long-acting duration effective antagonism rhesus monkeys.