RT Journal Article
SR Electronic
T1 Intranasal Delivery of Morphine
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 391
OP 400
DO 10.1124/jpet.301.1.391
VO 301
IS 1
A1 L. Illum
A1 P. Watts
A1 A. N. Fisher
A1 M. Hinchcliffe
A1 H. Norbury
A1 I. Jabbal-Gill
A1 R. Nankervis
A1 S. S. Davis
YR 2002
UL http://jpet.aspetjournals.org/content/301/1/391.abstract
AB Morphine administered nasally to humans as a simple solution is only absorbed to a limited degree, with a bioavailability of the order of 10% compared with intravenous administration. This article describes the development of novel nasal morphine formulations based on chitosan, which, in the sheep model, provide a highly increased absorption with a 5- to 6-fold increase in bioavailability over simple morphine solutions. The chitosan-morphine nasal formulations have been tested in healthy volunteers in comparison with a slow i.v. infusion (over 30 min) of morphine. The results show that the nasal formulation was rapidly absorbed with a Tmax of 15 min or less and a bioavailability of nearly 60%. The shape of the plasma profile for nasal delivery of the chitosan-morphine formulation was similar to the one obtained for the slow i.v. administration of morphine. Furthermore, the metabolite profile obtained after the nasal administration of the chitosan-morphine nasal formulation was essentially identical to the one obtained for morphine administered by the intravenous route. The levels of both morphine-6-glucuronide and morphine-3-glucuronide were only about 25% of that found after oral administration of morphine. It is concluded that a properly designed nasal morphine formulation (such as one with chitosan) can result in a noninjectable opioid product capable of offering patients rapid and efficient pain relief. The American Society for Pharmacology and Experimental Therapeutics