Claims for Patent: 11,583,216

Summary for Patent: 11,583,216

Title:	Method of administering sotalol IV/switch
Abstract:	Embodiments of the invention are broadly drawn to methods for determining an optimum dose of an antiarrhythmic drug, for example sotalol. In particular, the method involves titrating the dose of the drug gradually to determine the optimum plasma concentration for a patient, whether the patient has normal or abnormal renal function.
Inventor(s):	Vijay Ivaturi, Jogarao Gobburu
Assignee:	University of Maryland Baltimore
Application Number:	US17/003,297
Patent Claims:	1. A method for accelerated achievement of steady-state maximum plasma concentration of sotalol in a subject, comprising: 1) detecting a baseline QTc of the subject; 2) administering a first dose of the-antiarrhythmic drug sotalol to the subject via a first intravenous infusion for first duration of time to produce a change in QTc of no more than about 30 msec higher than baseline and a QTc of not more than 500 msec, then 3) determining the difference between the baseline QTc and a first QTc measured after the first intravenous infusion to detect a first delta QTc, and 4) if the first delta QTc is in a range of less than 20% from the baseline QTc, then administering to the subject a second dose of sotalol via a second intravenous infusion for a second duration of time, 5) or if the first delta QTc is in a range not within 20% of the baseline QTc, then discontinuing intravenous administration to the subject and administering any further doses of sotalol orally to the subject, wherein the subject has achieved a steady-state maximum plasma concentration of sotalol in an accelerated manner, to produce a maximum final delta QTc from baseline in the subject of a maximum of about 30 msec. 2. The method of claim 1, further comprising 6) measuring a second QTc after the second intravenous infusion, and determining the difference between the baseline QTc and the second QTc to detect a second delta QTc, wherein if the second delta QTc is in a range of less than 20% from the baseline QTc, then administering to the subject a third dose of sotalol via a third intravenous infusion for a third duration of time, or 7) if the second delta QTc is in a range not within 20% of the baseline QTc, then discontinuing intravenous administration and administering any further doses of sotalol orally to the subject, to produce a maximum final delta QTc from baseline in the subject of a maximum of about 30 msec. 3. The method of claim 2, further comprising measuring a third QTc after the third intravenous infusion, determining the difference between the baseline QTc and the third QTc to detect a third delta QTc, wherein if the third delta QTc is in a range of less than 20% from the baseline QTc, then administering any further doses of sotalol orally to the subject. 4. The method of claim 1, wherein the subject has normal or abnormal renal function and the first dose of the antiarrhythmic drug is 10 mg-60 mg administered via the first intravenous infusion. 5. The method of claim 1, wherein the first duration is 0.5 hour-2 hours. 6. The method of claim 1, wherein the subject has normal or abnormal renal function, the first delta QTc is not in the acceptable range and a dose of 75 mg, 80 mg, 120 mg, or 160 mg of sotalol is administered orally 0.5 to 2 hours after the start of the first infusion. 7. The method of claim 1, wherein the subject has normal renal function, the first delta QTc is in the acceptable range, and a second IV dose of 10-40 mg of sotalol is administered via the second intravenous infusion started 0.5 hours after the start of the first intravenous infusion, and lasting 0.5 to 2 hours. 8. The method of claim 1, wherein the subject has abnormal renal function, the first delta QTc is in the acceptable range, and a second dose of 5-30 mg of sotalol is administered via the second intravenous infusion. 9. The method of claim 8, wherein the second intravenous infusion dose is administered over 0.5 hour-2 hours, 0.5 hour-2 hours after the start of the first intravenous infusion. 10. The method of claim 2, wherein the second delta QTc is in a range not within 20% of the baseline QTc, intravenous infusion is discontinued and a dose of 120 mg of sotalol is administered orally after the second intravenous infusion, within 0.5 hours to 2 hours from the start of the first intravenous infusion. 11. The method of claim 2, wherein the second delta QTc is in a range of less than 20% from the baseline QTc and a third dose of 10-30 mg of sotalol is administered via a third intravenous infusion. 12. The method of claim 11, wherein the third intravenous infusion is administered over 0.5 hours, within 1 hour to 2 hours from the start of the first intravenous infusion. 13. The method of claim 12, wherein the third intravenous infusion is followed by a dose of 160 mg of sotalol administered orally after the third intravenous infusion and 1-3 hours after the start of the first infusion. 14. The method of claim 11, wherein the second QTc is in a range of less than 20% from the baseline QTc and a third dose of 10 mg of sotalol is administered via a third intravenous infusion over 0.5 hours, within 1-3 hours from the start of the first intravenous infusion. 15. The method of claim 12, wherein the third intravenous infusion is followed by a dose of 80 mg, 120 mg, or 160 mg of sotalol orally after the third intravenous infusion and 2 hours after the start of the first infusion. 16. The method of claim 7, wherein the subject has normal renal function, and a first maintenance dose of 80 mg of sotalol is orally administered 12 hours from initiation of the first infusion, and every 12 hours following the first maintenance dose. 17. The method of claim 8, wherein the subject has abnormal renal function, and a first maintenance dose of 80 mg of sotalol is orally administered 24 hours from initiation of the first infusion, and every 24 hours from the first maintenance dose. 18. The method of claim 7, wherein a maintenance dose of 120 mg of sotalol is orally administered every 12 hours from initiation of the first intravenous infusion. 19. The method of claim 10, wherein a maintenance dose of 120 mg of sotalol is orally administered every 24 hours from initiation of the first intravenous infusion. 20. The method of claim 11, wherein a maintenance dose of 160 mg of sotalol is orally administered every 12 hours from initiation of the first intravenous infusion. 21. The method of claim 14, wherein a maintenance dose of 160 mg of sotalol is orally administered every 24 hours from initiation of the first intravenous infusion. 22. The method of claim 1, wherein the subject has normal renal function and a maintenance dose of the antiarrhythmic drug is orally administered once every 12 hours after IV infusion is terminated. 23. The method of claim 1, wherein the subject has abnormal renal function and a maintenance dose of sotalol is orally administered once every 24 hours after IV infusion is terminated. 24. The method of claim 7, wherein the subject has normal renal function, and any further intravenous or oral dose of the drug is administered 12 hours after initiation of the first intravenous infusion. 25. The method of claim 8, wherein the subject has abnormal renal function, and any further intravenous or oral dose of the drug is administered 24 hours after initiation of the first intravenous infusion. 26. The method of claim 1 wherein the steady-state maximum plasma concentration is achieved in about 2.5 to 3 days. 27. A method for accelerated achievement of steady-state maximum plasma concentration of sotalol in a subject, comprising: 1) detecting a baseline QTc of the subject; 2) administering a first dose of the antiarrhythmic drug sotalol to the subject via a first intravenous infusion for a first duration of time, then 3) determining the difference between the baseline QTc and a first QTc measured after the first intravenous infusion to detect a first delta QTc, and 4) if the first delta QTc is range of less than 20% from the baseline QTc, then administering to the subject a second dose of sotalol via a second intravenous infusion for a second duration of time, 5) or if the first delta QTc is in a range not within 20% of the baseline QTc, then discontinuing intravenous administration to the subject or administering a reduced intravenous dose or doses until a delta QTc of less than 20% from the baseline QTc is reached, wherein the subject has achieved a steady-state maximum plasma concentration of sotalol in an accelerated manner, to produce a maximum final delta QTc from baseline in the subject of a maximum of about 30 msec. 28. The method of claim 27 wherein the steady-state maximum plasma concentration is achieved in about 1 day. 29. The method according to claim 27, further comprising 6) If the first delta QTc is in a range not within 20% of the baseline QTc and intravenous administration to the subject is discontinued, then administering any further doses of sotalol orally to the subject. 30. A method for accelerated achievement of steady-state maximum plasma concentration of sotalol in a subject, comprising: 1) detecting a baseline QTc of the subject; 2) administering a first dose of the antiarrhythmic drug sotalol to the subject via a first intravenous infusion for a first duration of time, then 3) determining the difference between the baseline QTc and a first QTc measured after the first intravenous infusion to detect a first delta QTc, and 4) if the first delta QTc exceeds a predetermined threshold of greater than 20% of the baseline QTc, then discontinuing intravenous administration to the subject and administering any further doses of sotalol orally, or administering a reduced intravenous dose or doses until an acceptable delta QTc is reached, wherein the subject has achieved a steady-state maximum plasma concentration of sotalol in an accelerated manner, to produce a maximum final delta QTc from baseline in the subject of a maximum of about 30 msec.