US20100003193A1 - Unit dosage of apadenoson - Google Patents
Unit dosage of apadenoson Download PDFInfo
- Publication number
- US20100003193A1 US20100003193A1 US12/496,949 US49694909A US2010003193A1 US 20100003193 A1 US20100003193 A1 US 20100003193A1 US 49694909 A US49694909 A US 49694909A US 2010003193 A1 US2010003193 A1 US 2010003193A1
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- US
- United States
- Prior art keywords
- unit dose
- apadenoson
- amount
- saline
- buffer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 229950001316 apadenoson Drugs 0.000 title claims abstract description 40
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Images
Classifications
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7076—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
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- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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Definitions
- the present invention relates to a unit dosage of Apadenoson, a pharmacological stress agent, and use of the same as a pharmacologic agent for myocardial perfusion imaging.
- Apadenoson shown below, was first described as a pharmacologic stress agent
- Dr. Hendel et al reported to the American Heart Association on the preliminary results of 127 patient SPECT Tc 99m sestamibi imaging studying comparing adenosine with Apadenoson using either 1 ⁇ g/kg or 2 ⁇ g/kg intravenous boluses of Apadenoson. The report concluded that Apadenoson was safe and well-tolerated and worthy of Phase III evaluation. In 2006, Dr.
- Kern et al reported to the American Heart Association the results of a Phase II study of Apadenoson, one goal of which was to determine an appropriate dose for Phase III clinical trials.
- Intravenous bolus dosages of 0.5, 1.0, 2.0, and 2.5 ⁇ g/kg were studied.
- the average peak velocity for coronary blood flow was shown to increase with a corresponding increase in dosage from 0.5 to 2 ⁇ g/kg (see FIG. 1 ).
- Apadenoson would need to be administered on a weight basis, not a unit dose basis.
- the present invention provides a novel unit dose of Apadenoson suitable for parenteral administration.
- the present invention also provides a novel method of diagnosing myocardial dysfunction using a unit dose of Apadenoson as a pharmacologic stress agent.
- FIG. 1 shows the average peak flow wire velocity of one patient from a Phase II clinical trial study.
- adenosine was administered by intracoronary injection, and coronary blood flow velocity was monitored with a flow wire.
- the three injections of adenosine increased blood flow velocity consistent with the well characterized pharmacology of adenosine.
- increasing bolus doses of Apadenoson at doses shown to be safe, achieved peak flow equivalent to adenosine.
- FIG. 2 shows the average peak flow wire velocity of 33 patients from the study described in FIG. 1 .
- CBFV coronary blood flow velocity
- the present invention provides a novel unit dose of Apadenoson, comprising: (a) Apadenoson and (b) a pharmaceutically acceptable carrier, wherein the unit dose is suitable for parenteral administration.
- the unit dose is suitable for intravenous administration.
- the amount of Apadenoson present in the unit dose is selected from 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158,
- the amount of Apadenoson present in the unit dose is in the range selected from 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, to 125 ⁇ g. Additional examples of the weight of Apadenoson present include (a) 115, 120, and 125 ⁇ g and (b) 120 ⁇ g.
- the pharmaceutical carrier comprises: a cyclodextrin.
- cyclodextrins include ⁇ -CD or derivatives thereof (e.g., ⁇ -hydroxypropyl-CD (HP- ⁇ -CD)), ⁇ -CD or derivatives thereof (e.g., ⁇ -hydroxypropyl-CD (HP- ⁇ -CD), methylated ⁇ -cyclodextrin, hydroxyethyl- ⁇ -cyclodextrin, and sulfobutylether ⁇ -CD), and ⁇ -CD or derivatives thereof (e.g., ⁇ -hydroxypropyl-CD (HP- ⁇ -CD)).
- concentration of CD examples include being within the range selected from (a) about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10% w/v; (b) about 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, to 4% w/v; (c) about 1% w/v; and, (d) about 2% w/v of the final formulation.
- CD e.g., hydroxypropyl- ⁇ -cyclodextrin
- the pharmaceutical carrier comprises: buffered saline.
- a useful buffer is a citrate buffer (e.g., sodium citrate).
- Citric acid can be useful to adjust the pH of the unit dose.
- the pharmaceutical carrier comprises: buffered saline, comprising: saline, sodium citrate, and citric acid.
- buffered saline comprising: saline, sodium citrate, and citric acid.
- citric acid may not be present in the final unit dose due to ionization.
- the pH of the unit dose is selected from 4.6, 4.7, 4.8, 4.9, to 5.0.
- Another example of the pH of the unit does is 4.8.
- the volume of the unit dose is selected from 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, and 5 mL.
- Another example of the volume is from 2, 3, 4, to 5 mL.
- the unit dose comprises:
- the unit dose comprises:
- the unit dose comprises:
- the unit dose comprises:
- the unit dose of the present invention can be filled into any useful container for storage, transportation, and usage.
- An example of a useful container is a syringe body.
- the present invention provides a novel method of diagnosing myocardial perfusion abnormalities in a mammal, comprising:
- the patient weighs at least 40 kg.
- the administration is intravenous administration.
- the technique is an imaging technique selected from: planar or single photon emission computed tomography (SPECT), gamma camera scintigraphy, positron emission tomography (PET), nuclear magnetic resonance (NMR) imaging, magnetic resonance imaging (MRI) imaging, perfusion contrast echocardiography, digital subtraction angiography (DSA), and ultrafast X-ray computed tomography (CINE CT).
- SPECT planar or single photon emission computed tomography
- PET gamma camera scintigraphy
- PET positron emission tomography
- NMR nuclear magnetic resonance
- MRI magnetic resonance imaging
- DSA digital subtraction angiography
- CINE CT ultrafast X-ray computed tomography
- the present invention provides a prefilled syringe, comprising: a syringe and a unit dose of Apadenoson, comprising: (a) Apadenoson and (b) a pharmaceutically acceptable carrier, wherein the unit dose is suitable for parenteral administration.
- the syringe can be any known syringe useful for parenteral administration.
- the syringe can comprise: a body and a plunger movably disposed within the body.
- the body can be cylindrical with a first open end to receive the plunger and a second end opposite the first, with the second end modified with an opening sufficient for the unit dose to pass through.
- the syringe can further comprise: a needle (e.g., an injection needle).
- the needle can be detachably connected to or permanently fixed to the body.
- a needle guard can also be present
- the present invention provides a novel unit dose of Apadenoson for use in medical therapy.
- the present invention provides a novel use of a unit dose of Apadenoson for the manufacture of a medicament for use in diagnosing myocardial perfusion abnormalities in a mammal.
- the Apadenoson unit dose of the present invention can be administered as a pharmacological stress agent and used in conjunction with any one of several noninvasive diagnostic procedures to measure aspects of myocardial, coronary, and/or ventricular perfusion.
- Aspects that can be measured include coronary artery stenoses, myocardial dysfunction (e.g., myocardial ischemia, coronary artery disease, ventricular dysfunction, and differences in blood flow through disease-free coronary vessels and/or stenotic coronary vessels), myocardial contractile dysfunction, the presence of regional wall motion abnormalities, the functional significance of stenotic coronary vessels, coronary artery disease, ischemic ventricular dysfunction, and vasodilatory capacity (reserve capacity) of coronary arteries in humans.
- myocardial dysfunction e.g., myocardial ischemia, coronary artery disease, ventricular dysfunction, and differences in blood flow through disease-free coronary vessels and/or stenotic coronary vessels
- myocardial contractile dysfunction e.
- Radiopharmaceuticals are typically used in diagnostic method methods.
- the radiopharmaceutical agent may comprise, for example, a radionuclide selected from the group consisting of thallium-201, technetium-99 m , nitrogen-13, rubidium-82, iodine-123 and oxygen-15.
- Unit dose means the amount of a medication administered to a patient in a single dose.
- a unit dose is typically independent of the weight of the patient or may be associated with a specified weight range (e.g., ⁇ 40kg).
- Mammal and patient covers warm blooded mammals that are typically under medical care (e.g., humans and domesticated animals). Examples of mammals include (a) feline, canine, equine, and bovine and (b) human.
- Parenteral includes intravenous, intramuscular, and subcutaneous routes.
- Sterile injectable solutions are typically prepared by incorporating the active compound in the required amount in the appropriate solvent with various of the other ingredients enumerated above, as required, followed by filter sterilization (or some other form of sterilization).
- filter sterilization or some other form of sterilization.
- the methods of preparation include vacuum drying and the freeze drying techniques, which yield a powder of the active ingredient plus any additional desired ingredient present in the previously sterile-filtered solutions.
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US12/496,949 US20100003193A1 (en) | 2008-07-03 | 2009-07-02 | Unit dosage of apadenoson |
US13/544,364 US20130017153A1 (en) | 2008-07-03 | 2012-07-09 | Unit dosage of apadenoson |
US14/103,130 US9415058B2 (en) | 2008-07-03 | 2013-12-11 | Unit dosage of Apadenoson |
US15/181,235 US9662406B2 (en) | 2008-07-03 | 2016-06-13 | Unit dosage of apadenoson |
US15/600,303 US20170252463A1 (en) | 2008-07-03 | 2017-05-19 | Unit dosage of apadenoson |
US16/045,359 US20190022253A1 (en) | 2008-07-03 | 2018-07-25 | Unit dosage of apadenoson |
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US7816908P | 2008-07-03 | 2008-07-03 | |
US15593709P | 2009-02-27 | 2009-02-27 | |
US12/496,949 US20100003193A1 (en) | 2008-07-03 | 2009-07-02 | Unit dosage of apadenoson |
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US13/544,364 Continuation US20130017153A1 (en) | 2008-07-03 | 2012-07-09 | Unit dosage of apadenoson |
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US20100003193A1 true US20100003193A1 (en) | 2010-01-07 |
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US13/544,364 Abandoned US20130017153A1 (en) | 2008-07-03 | 2012-07-09 | Unit dosage of apadenoson |
US14/103,130 Expired - Fee Related US9415058B2 (en) | 2008-07-03 | 2013-12-11 | Unit dosage of Apadenoson |
US15/181,235 Active US9662406B2 (en) | 2008-07-03 | 2016-06-13 | Unit dosage of apadenoson |
US15/600,303 Abandoned US20170252463A1 (en) | 2008-07-03 | 2017-05-19 | Unit dosage of apadenoson |
US16/045,359 Abandoned US20190022253A1 (en) | 2008-07-03 | 2018-07-25 | Unit dosage of apadenoson |
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US13/544,364 Abandoned US20130017153A1 (en) | 2008-07-03 | 2012-07-09 | Unit dosage of apadenoson |
US14/103,130 Expired - Fee Related US9415058B2 (en) | 2008-07-03 | 2013-12-11 | Unit dosage of Apadenoson |
US15/181,235 Active US9662406B2 (en) | 2008-07-03 | 2016-06-13 | Unit dosage of apadenoson |
US15/600,303 Abandoned US20170252463A1 (en) | 2008-07-03 | 2017-05-19 | Unit dosage of apadenoson |
US16/045,359 Abandoned US20190022253A1 (en) | 2008-07-03 | 2018-07-25 | Unit dosage of apadenoson |
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US (6) | US20100003193A1 (pl) |
EP (1) | EP2306971B1 (pl) |
JP (2) | JP2011526894A (pl) |
KR (2) | KR20110028531A (pl) |
CN (1) | CN102119023B (pl) |
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CY (1) | CY1116283T1 (pl) |
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EA (1) | EA022348B1 (pl) |
ES (1) | ES2537069T3 (pl) |
HK (1) | HK1156250A1 (pl) |
HR (1) | HRP20150454T1 (pl) |
IL (2) | IL210428A (pl) |
MX (1) | MX2011000193A (pl) |
MY (1) | MY161655A (pl) |
NZ (1) | NZ590489A (pl) |
PL (1) | PL2306971T3 (pl) |
PT (1) | PT2306971E (pl) |
SI (1) | SI2306971T1 (pl) |
SM (1) | SMT201500123B (pl) |
WO (1) | WO2010002473A1 (pl) |
ZA (1) | ZA201100163B (pl) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013114204A1 (en) | 2012-02-03 | 2013-08-08 | Adenobio N.V. | A method of using adenosine and dipyridamole for pharmacologic stress testing, with specific compositions, unit dosage forms and kits |
US9415058B2 (en) | 2008-07-03 | 2016-08-16 | University Of Virginia Patent Foundation | Unit dosage of Apadenoson |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109020881B (zh) * | 2018-06-28 | 2020-04-28 | 新发药业有限公司 | 一种阿帕替尼的制备方法 |
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2009
- 2009-07-02 CN CN200980131395.6A patent/CN102119023B/zh not_active Expired - Fee Related
- 2009-07-02 EA EA201100132A patent/EA022348B1/ru not_active IP Right Cessation
- 2009-07-02 KR KR1020117002495A patent/KR20110028531A/ko active Application Filing
- 2009-07-02 CA CA2729819A patent/CA2729819C/en active Active
- 2009-07-02 BR BRPI0913939A patent/BRPI0913939A2/pt not_active Application Discontinuation
- 2009-07-02 EP EP09773926.2A patent/EP2306971B1/en active Active
- 2009-07-02 US US12/496,949 patent/US20100003193A1/en not_active Abandoned
- 2009-07-02 WO PCT/US2009/003939 patent/WO2010002473A1/en active Application Filing
- 2009-07-02 PT PT97739262T patent/PT2306971E/pt unknown
- 2009-07-02 KR KR1020147003142A patent/KR20140021726A/ko not_active Application Discontinuation
- 2009-07-02 DK DK09773926.2T patent/DK2306971T3/en active
- 2009-07-02 PL PL09773926T patent/PL2306971T3/pl unknown
- 2009-07-02 JP JP2011516343A patent/JP2011526894A/ja not_active Withdrawn
- 2009-07-02 AU AU2009266317A patent/AU2009266317B2/en not_active Ceased
- 2009-07-02 MY MYPI2010006339A patent/MY161655A/en unknown
- 2009-07-02 NZ NZ590489A patent/NZ590489A/xx not_active IP Right Cessation
- 2009-07-02 ES ES09773926.2T patent/ES2537069T3/es active Active
- 2009-07-02 SI SI200931189T patent/SI2306971T1/sl unknown
- 2009-07-02 MX MX2011000193A patent/MX2011000193A/es active IP Right Grant
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2011
- 2011-01-02 IL IL210428A patent/IL210428A/en not_active IP Right Cessation
- 2011-01-06 ZA ZA2011/00163A patent/ZA201100163B/en unknown
- 2011-10-07 HK HK11110662.3A patent/HK1156250A1/xx not_active IP Right Cessation
-
2012
- 2012-07-09 US US13/544,364 patent/US20130017153A1/en not_active Abandoned
-
2013
- 2013-08-29 JP JP2013177622A patent/JP2013237702A/ja active Pending
- 2013-12-11 US US14/103,130 patent/US9415058B2/en not_active Expired - Fee Related
-
2015
- 2015-04-27 HR HRP20150454TT patent/HRP20150454T1/hr unknown
- 2015-05-14 CY CY20151100432T patent/CY1116283T1/el unknown
- 2015-05-22 SM SM201500123T patent/SMT201500123B/xx unknown
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2016
- 2016-05-10 IL IL245577A patent/IL245577B/en active IP Right Grant
- 2016-06-13 US US15/181,235 patent/US9662406B2/en active Active
-
2017
- 2017-05-19 US US15/600,303 patent/US20170252463A1/en not_active Abandoned
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2018
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9415058B2 (en) | 2008-07-03 | 2016-08-16 | University Of Virginia Patent Foundation | Unit dosage of Apadenoson |
US9662406B2 (en) | 2008-07-03 | 2017-05-30 | University Of Virginia Patent Foundation | Unit dosage of apadenoson |
WO2013114204A1 (en) | 2012-02-03 | 2013-08-08 | Adenobio N.V. | A method of using adenosine and dipyridamole for pharmacologic stress testing, with specific compositions, unit dosage forms and kits |
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