Pharmacokinetics of iontophoretic sumatriptan administration

Abstract

Improved pharmacokinetic profiles for the iontophoretic delivery of sumatriptan are described.

1 . A method for treating a sumatriptan responsive state in a subject, comprising iontophoretically administering to said subject an amount of a sumatriptan using a current of 3.5 mA or greater for at least a portion of the treatment period, such that said sumatriptan responsive state in said subject is treated. 
     
     
         2 . The method of  claim 1 , wherein said current is 4.0 mA or greater. 
     
     
         3 . The method of  claim 1  or  2 , wherein said portion of said treatment period is about thirty minutes to about 90 minutes. 
     
     
         4 . The method of any one of  claims 1 - 3 , wherein said method further comprises a low current treatment period using a current of between about 1.5 to about 2.5 mA. 
     
     
         5 . The method of  claim 4 , wherein said low current treatment period uses a current of about 2.0 mA. 
     
     
         6 . The method of  claim 4  or  5 , wherein said low current treatment period is between about 2 hours and about 4 hours in length. 
     
     
         7 . A method for treating a sumatriptan responsive state in a subject, comprising iontophoretically administering to said subject an amount of an effective amount of sumatriptan using a current of about 4 mA for a high current treatment period of about one hour and a current of about 2 mA for a subsequent low current treatment period, such that said subject is treated for said sumatriptan responsive state. 
     
     
         8 . The method of  claim 7 , wherein said amount of sumatriptan is about 10 mg. 
     
     
         9 . A method for treating a sumatriptan responsive state in a subject, comprising administering to said subject an amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said amount of sumatriptan results in an AUC 0-inf  with a 95% confidence interval between about 99 and 128 hr*ng/mL and a C max  with a 95% confidence interval between about 20 to about 28 ng/mL. 
     
     
         10 . The method of  claim 9 , wherein said sumatriptan is administered iontophoretically. 
     
     
         11 . The method of  claims 9  or  10 , wherein about 10 mg of sumatriptan is administered to said subject. 
     
     
         12 . A method for treating a sumatriptan responsive state in a subject, comprising iontphoretically administering to said subject an amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said amount of sumatriptan results in an AUC 0-inf  within a 95% confidence interval between about 99 and about 128 hr*ng/mL. 
     
     
         13 . A method for treating a sumatriptan responsive state in a subject, comprising iontphoretically administering to said subject an amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said amount of sumatriptan results in an AUC 0-inf  between about 99 and about 128 hr*ng/mL. 
     
     
         14 . A method for treating a sumatriptan responsive state in a subject, comprising iontophoretically administering to said subject an amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said amount of sumatriptan results in a C max  within a 95% confidence interval between about 20 and about 28 ng/mL. 
     
     
         15 . A method for treating a sumatriptan responsive state in a subject, comprising iontophoretically administering to said subject an amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said sumatriptan is administered such that a C max  of about 23-25 ng/mL is achieved and plasma concentrations are sustained for at least three hours. 
     
     
         16 . A method for treating a sumatriptan responsive state in a subject, comprising administering to said subject an amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said amount of sumatriptan results in an AUC 0-inf  between about 99 and 128 hr*ng/mL and a C max  between about 20 to about 28 ng/mL. 
     
     
         17 . The method of any one of  claims 12 - 16 , wherein said sumatriptan is administered using current of at least about 3.5 mA for between about thirty minutes and ninety minutes. 
     
     
         18 . The method of  claim 17 , wherein said sumatriptan is administered using a current of at least about 4 mA. 
     
     
         19 . The method of any one of  claims 12 - 18 , wherein said sumatriptan is administered using a current of about 1.5 mA to about 2.5 mA for between about two to about six hours. 
     
     
         20 . The method of any one of  claims 12 - 19 , wherein said sumatriptan is administered using a current of about 4 mA for a period of about one hour and subsequently a current of about 2.0 mA for a period of about three hours. 
     
     
         21 . The method of any one of  claims 1 - 20 , wherein said sumatriptan is administered iontophoretically using a iontophoretic patch. 
     
     
         22 . The method of  claim 21 , wherein said iontophoretic patch is integrated. 
     
     
         23 . A method for treating a sumatriptan responsive state in a subject, comprising administering to said subject an effective amount of sumatriptan using an iontophoretic patch for an effective treatment period, such that said sumatriptan responsive state in said subject is treated, wherein said patch employs a current density of at least about 0.10 mA/cm 2  or higher for at least a portion of said treatment period. 
     
     
         24 . The method of  claim 23 , wherein said patch has an iontophoretically active surface area of about 10 cm 2  or greater. 
     
     
         25 . The method of  claim 24 , wherein said surface area is about 30 cm 2 . 
     
     
         26 . The method of any one of  claims 22 - 25 , wherein said treatment period comprises a high current density period and a low current density period. 
     
     
         27 . The method of  claim 26 , wherein the current density of said high current density period is between about 0.10 mA/cm 2  and 0.5 mA/cm 2 . 
     
     
         28 . The method of  claim 26  or  27 , wherein said high current density period is about 30 minutes to about 90 minutes. 
     
     
         29 . The method of any one of  claims 26 - 28 , wherein a current of about 3 mA to about 5 mA is used during said high current density period. 
     
     
         30 . The method of  claim 26 , wherein said current density of said low current density period is between about 0.03 mA/cm 2  and 0.20 mA/cm 2 . 
     
     
         31 . The method of  claim 30 , wherein said current density of said low current density period is about 0.03 mA/cm 2  to about 0.15 mA/cm 2 . 
     
     
         32 . The method of  claim 30  or  31 , wherein said low current density period is about 2.5 to 6 hours. 
     
     
         33 . The method of any one of  claims 30 - 33 , wherein a current of about 1.25 mA to about 2.5 mA is used during said low current density period. 
     
     
         34 . The method of any one of  claims 26 - 33 , wherein said high current density period precedes said low current density period. 
     
     
         35 . The method of any one of  claims 22 - 34 , wherein a therapeutic plasma level occurs in less than one hour after the beginning of said treatment period. 
     
     
         36 . The method of any one of  claims 22 - 37 , wherein effective amount of sumatriptan is about 10 ng/mL to about 28 ng/mL in said subject's plasma. 
     
     
         37 . A method for treating a subject for a sumatriptan responsive state, comprising administering to said subject an effective amount of sumatriptan using an iontophoretic patch for an effective treatment period comprising a high current density period and a low current density period, such that said subject is treated for said sumatriptan responsive state, wherein said high current density period has a current density of between about 0.10 mA/cm 2  and about 0.30 mA/cm 2  and said low current density period has a current density of about 0.05 mA/cm 2  and about 0.15 mA/cm 2 . 
     
     
         38 . A method for treating a subject for a sumatriptan responsive state, comprising administering to said subject an effective amount of sumatriptan using an iontophoretic patch for an effective treatment period comprising a high current density period and a low current density period, such that said subject is treated for said sumatriptan responsive state, wherein said high current density period has a current density of between about 0.13 mA/cm 2  and about 0.4 mA/cm 2  and said low current density period has a current density of between about 0.067 mA/cm 2  and about 0.2 mA/cm 2 . 
     
     
         39 . The method of any one of  claims 22 - 38 , wherein said high current density period is about one hour. 
     
     
         40 . The method of  claims 22 - 39 , wherein said low current density period is at least about three hours or longer. 
     
     
         41 . The method of  claim 40 , wherein said low current density period is at least about five hours or longer. 
     
     
         42 . The method of any one of  claims 22 - 41 , wherein the AUC 0-inf  is about 99 hr*ng/mL to about 128 hr*ng/mL. 
     
     
         43 . The method of any one of  claims 22 - 42 , wherein t 1/2  is about 2 hours to about 3.5 hours. 
     
     
         44 . A method for treating a subject for a sumatriptan responsive state, comprising transdermally administering to said subject an effective amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said effective amount of sumatriptan is administered without substantial adverse effects. 
     
     
         45 . The method of  claim 44 , wherein said sumatriptan is administered iontophoretically. 
     
     
         46 . The method of  claim 44  or  45 , wherein said adverse effects comprise pain, pressure sensations or atypical sensations. 
     
     
         47 . The method of  claim 44 , wherein said sumatriptan is administered such that an AUC 0-inf  is achieved with a 95% confidence interval between 99 and 128 hr*ng/mL. 
     
     
         48 . The method of any one of  claims 44 - 49 , wherein said sumatriptan is administered such that a C max  is achieved with a 95% confidence interval between about 20 ng/mL and about 28 ng/mL. 
     
     
         49 . The method of  claim 44 , wherein said sumatriptan is administered such that an AUC 0-inf  is between 99 and 128 hr*ng/mL. 
     
     
         50 . The method of  claim 44 , wherein said sumatriptan is administered such that a C max  is between about 20 ng/mL and about 28 ng/mL. 
     
     
         51 . A method of treating a sumatriptan responsive state in a subject, comprising transdermally administering to said subject an effective amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said administration of sumatriptan results in an AUC 0-inf , t 1/2 , or C max  coefficient of variance (CV) of less than about 25%. 
     
     
         52 . The method of  claim 51 , wherein said sumatriptan is administered iontophoretically. 
     
     
         53 . The method of  claim 52 , wherein said sumatriptan is administered using a iontophoretic patch. 
     
     
         54 . A method of treating a sumatriptan responsive state in a subject, comprising transdermally administering to said subject an effective amount of sumatriptan, such that said sumatriptan responsive state is treated, wherein said administration of sumatriptan results in an AUC 0-inf  in coefficient of variance less than twice the AUC 0-inf  coefficient of variance for subcutaneous administration of sumatriptan for a similar sample size. 
     
     
         55 . The method of any one of  claims 1 - 54 , wherein said effective amount of sumatriptan is administered without substantially irritating said subject's skin. 
     
     
         56 . The method of  claim 55 , wherein said iontophoretic administration of sumatriptan causes little or no erythema. 
     
     
         57 . The method of  claim 55 , wherein said iontophoretic administration of sumatriptan causes little or no punctuate lesions. 
     
     
         58 . The method of any one of  claims 1 - 57 , wherein said sumatriptan responsive state is a migraine. 
     
     
         59 . The method of any one of  claims 1 - 58 , wherein said subject is a human. 
     
     
         60 . An iontophoretic patch, wherein said patch is designed to deliver sumatriptan such that the patch performs the methods of any one of  claims 1 - 59 .