title: Minor pathological changes are induced by naltrexone-poly(DL-lactide) implants in pregnant rats.
abstract: Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained-release preparations have been developed to overcome noncompliance. Many sustained-release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed; a single active tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13-26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose-dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low-level inflammation, suggested good long-term biocompatibility. We conclude that the Australian naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans.
authors.affiliation: Experimental and Regenerative Neurosciences, School of Animal Biology (M317), The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
authors.forename: W O
authors.initials: WO
authors.lastname: Farid
authors.forename: D
authors.initials: D
authors.lastname: McCallum
authors.forename: R J
authors.initials: RJ
authors.lastname: Tait
authors.forename: S A
authors.initials: SA
authors.lastname: Dunlop
authors.forename: G K
authors.initials: GK
authors.lastname: Hulse
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000494:pharmacology; D001718:Birefringence; D005260:Female; D005549:Foreign-Body Reaction / Q000473:pathology; D020007:Implants, Experimental / Q000009:adverse effects*; D007249:Inflammation / Q000473:pathology; D008297:Male; D009271:Naltrexone / Q000009:adverse effects* / Q000097:blood; D011091:Polyesters / Q000009:adverse effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D001672:Biocompatible Materials; D011091:Polyesters; C033616:poly(lactide); D009271:Naltrexone