Reference

Kinetics of a naltrexone sustained-release preparation

Kinetics of a naltrexone sustained-release preparation. Chiang, C. N.; Hollister, L. E.; Kishimoto, Akiri; Barnett, G. (Div. Preclin. Res., Natl. Inst. Drug Abuse, Rockville, MD 20857, USA). Clin. Pharmacol. Ther. (St. Louis), 36(5), 704-8 (English) 1984. CODEN: CLPTAT. ISSN: 0009-9236. DOCUMENT TYPE: Journal CA Section: 63 (Pharmaceuticals) A biodegradable sustained-release naltrexone (I) [16590-41-3] bead prepn. contg. 70% I in a phys. mixt. with a L-(+)-lactic acid-glycolic acid copolymer [54512-07-1] () was evaluated in 3 male subjects. Each subject received a 10-mg i.v. dose of I-HCl and a 63-mg dose by s.c. implantation of I beads. Kinetics of I estd. from the i.v. dose indicated a plasma clearance range of 3.1 to 3.4 L/min and a t1/2 range of 1.7-3.7 h. After bead implantation, av. plasma I levels were maintained at 0.3-0.4 ng/mL and naltrexol [20410-98-4] levels were at 0.4-1.0 ng/mL for approx. 1 mo, during which urine I and naltrexol levels were about 20-30 and 70-200 ng/mL. It was estd. that approx. 70-77% of the dose was absorbed after bead implantation. There were no serious adverse effects other than tissue irritation in 2 of the three subjects.

Discriminative stimulus effects of morphine withdrawal in the dependent rat: suppression by opiate and nonopiate drugs

Discriminative stimulus effects of morphine withdrawal in the dependent rat: suppression by opiate and nonopiate drugs. Holtzman, Stephen G. (Sch. Med., Emory Univ., Atlanta, GA, USA). J. Pharmacol. Exp. Ther., 233(1), 80-6 (English) 1985. CODEN: JPETAB. ISSN: 0022-3565. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Opiate and nonopiate drugs were injected s.c. and examd. for their ability to block naltrexone [16590-41-3]-induced discriminative effects and loss of body wt. in morphine [57-27-2]-dependent rats. Seven opiates blocked dose-dependently the discriminative effects of naltrexone and loss of body wt. Potency ranged from fentanyl citrate [990-73-8] (330 ′ morphine) to meperidine [57-42-1] (<1 ′ morphine); effects were stereoselective for levorotatory isomers. Loperamide [53179-11-6], an opiate that does not readily enter the brain, blocked loss of body wt. but not discriminative effects, suggesting that discriminative effects are mediated centrally. Nonopiate behavioral depressants, diazepam [439-14-5], haloperidol [52-86-8] and pentobarbital [76-74-4], did not substantially affect either dependent variable, but clonidine [4205-90-7] (0.01-1.0 mg/kg) blocked discriminative effects of naltrexone partially and wt. loss completely. The blockade by morphine (30 mg/kg) of naltrexone-induced discriminative effects and wt. loss was surmounted by increasing the dose of naltrexone whereas the blockade by clonidine (0.1 mg/kg) was not. Thus, blockade by opiates of effects of naltrexone appears to be due to a competitive interaction at the mu opioid receptor; clonidine has a different mechanism of action. This discriminative paradigm may afford a specific animal model for studying fundamental processes underlying phys. dependence on opiates and for evaluating novel pharmacol. approaches for treating opiate withdrawal in humans.