PT  - JOURNAL ARTICLE
AU  - L. Illum
AU  - P. Watts
AU  - A. N. Fisher
AU  - M. Hinchcliffe
AU  - H. Norbury
AU  - I. Jabbal-Gill
AU  - R. Nankervis
AU  - S. S. Davis
TI  - Intranasal Delivery of Morphine
AID  - 10.1124/jpet.301.1.391
DP  - 2002 Apr 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 391--400
VI  - 301
IP  - 1
4099  - http://jpet.aspetjournals.org/content/301/1/391.short
4100  - http://jpet.aspetjournals.org/content/301/1/391.full
SO  - J Pharmacol Exp Ther2002 Apr 01; 301
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