ADENOSINE DERIVATIVE FORMULATIONS FOR MEDICAL IMAGING
A stable composition useful for myocardial perfusion imaging contains one or more 2-alkynyladenosine derivatives; and a solvent which is made up of water and hydroxypropyl-β-cyclodextrin.
1 . A stable composition useful for myocardial perfusion imaging, comprising:
(a) an adenosine derivative, which is methyl trans-4-[3-[6-amino-9-(N-ethyl-β-D-ribofuranosyluronamide)-9H-purin-2-yl]prop-2-ynyl]cyclohexane carboxylate or a pharmaceutically acceptable salt thereof; and,
(b) a solvent consisting essentially of water and hydroxypropyl-β-cyclodextrin.
2 . The composition of claim 1 , further comprising a buffer.
3 . The composition of claim 2 , wherein the buffer comprises: sodium citrate and citric acid.
4 . The composition of claim 1 , wherein the concentration of hydroxypropyl-β-cyclodextrin is about 0.1-10% w/v.
5 . The composition of claim 4 , wherein the concentration of hydroxypropyl-β-cyclodextrin is about 0.5-2% w/v.
6 . The composition of claim 1 , wherein the molar ratio of the adenosine derivative to hydroxypropyl-β-cyclodextrin is about 1:30 to 1:150.
7 . The composition of claim 1 , wherein hydroxyethyl-β-cyclodextrin is absent from the composition.
8 . The composition of claim 1 , wherein any other β-cyclodextrin is absent from the composition.
9 . The composition of claim 1 , wherein any other solvent is absent from the composition.
10 . The composition of claim 1 , wherein the composition is storage stable for at least about 3 months.
11 . A method of inducing cardiovascular stress, which comprises administering to a patient a pharmacologic vasodilation formulation, comprising:
(a) an adenosine derivative, which is methyl trans-4-[ 3 -[6-amino-9-(N-ethyl-β-D-ribofuranosyluronamide)-9H-purin-2-yl]prop-2-ynyl]cyclohexane carboxylate or a pharmaceutically acceptable salt thereof,
(b) a solvent consisting essentially of water and hydroxypropyl-β-cyclodextrin; and,
(c) buffer.
12 . The method of claim 11 , wherein the composition is administered intravenously.
13 . The method of claim 11 , wherein the adenosine derivative is administered at a dose not exceeding about 5 mcg/kg of body weight.
14 . The method of claim 13 , wherein the adenosine derivative is administered at a dose not exceeding about 2 mcg/kg of body weight.
15 . The method of claim 11 , wherein the adenosine derivative is administered at a dose within the range of about 0.5-5 mcg/kg.
16 . The method of claim 11 , wherein the adenosine derivative is administered via an intracoronary route to the human in a dose of about 0.05-0.5 mcg thereof sufficient to provide coronary artery dilation.
17 . A cardiovascular stress testing kit, comprising:
(a) an adenosine derivative, which is methyl trans-4-[3-[6-amino-9-(N-ethyl-β-D-ribofuranosyluronamide)-9H-purin-2-yl]prop-2-ynyl]cyclohexane carboxylate or a pharmaceutically acceptable salt thereof; and,
(b) a solvent consisting essentially of water and hydroxypropyl-β-cyclodextrin.
18 . The kit of claim 17 , wherein hydroxyethyl-β-cyclodextrin is absent from the solvent.