title: Extended-release formulation of morphine for subcutaneous administration.
abstract: Pain arising from cancer tends to be chronic and chemotherapy of cancer pain usually requires narcotics. Most injectable narcotics, however, have short half-lives (T1/2) and require either continuous infusion or repeated frequent injections which are both inconvenient and uncomfortable. An extended-release formulation of morphine sulfate (Depo/Morphine) in a lipid-based drug-delivery system was characterized and tested in an animal model. The encapsulation efficiency was 53% +/- 4%, and the in vitro release T1/2 in human plasma at 37 degrees C was 12.1 +/- 1.1 days. Following s.c. administration of Depo/Morphine, the total amount of morphine remaining at the s.c. injection site decreased monoexponentially with a T1/2 value of 2.59 +/- 0.16 days as compared with 0.46 +/- 0.04 h following the injection of unencapsulated morphine. The morphine concentration in plasma also decreased monoexponentially with a T1/2 value of 8.33 +/- 2.13 days as compared with 0.45 +/- 0.21 h for unencapsulated morphine. Cataleptic behavior was observed in mice injected with unencapsulated morphine but not in those given an identical dose of morphine in the form of Depo/Morphine. In conclusion, Depo/Morphine has potential as an extended-release formulation of morphine and may be useful in chemotherapy of cancer pain as well as in maintenance therapy of narcotic addicts.
authors.affiliation: Department of Medicine, University of California, San Diego, La Jolla 92093-0812.
authors.forename: T
authors.initials: T
authors.lastname: Kim
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006801:Humans; D007279:Injections, Subcutaneous; D008051:Lipid Bilayers; D051379:Mice; D009020:Morphine / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology; D010146:Pain / Q000188:drug therapy*
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008051:Lipid Bilayers; D009020:Morphine