Granted Patent B2

US 12,414,943 · App. 18/195,747 · Granted Sep 16, 2025

Inventors: S. George Kottayil (West Windsor, NJ); Amresh Kumar (Plainsboro, NJ); Prasanna Sunthankar (West Windsor, NJ); Kamalkishore Pati (Old Bridge, NJ); Vimal Kavuru (Holmdel, NJ)

Assignee: Grace Therapeutics U.S., Inc.

A61K31/4422A61K9/0029A61K9/1075A61K47/10A61K47/26A61K47/40A61K47/44

Abstract

Claims (18)

1. A method of providing an IV nimodipine infusion regimen in a human, comprising intravenously administering over at least a 24-hour period (i) a continuous intravenous nimodipine infusion supplemented with (ii) intravenous bolus administrations of nimodipine at a set interval, thereby providing a 24-hour AUC and C max of nimodipine that are equivalent to the 24-hour AUC and C max of a 30 mg or 60 mg oral nimodipine dose administered orally at about 4-hour intervals over the at least a 24-hour period.

2. The method of claim 1 , wherein the IV nimodipine infusion regimen is administered for a time period longer than 24 hours.

3. The method of claim 1 , wherein the continuous intravenous nimodipine infusion is at a rate of about 0.15 mg/hour of nimodipine infused intravenously over the 24-hour period, and supplemented with the intravenous bolus administrations of about 4 mg nimodipine infused over about 30 minute at about 4 hour intervals over the 24-hour period, such that the IV nimodipine infusion regimen provides the 24 hour AUC and C max of nimodipine that are equivalent to the 24-hour area under the curve and the 24-hour C max of the 60 mg nimodipine administered orally at about 4-hour intervals over the 24-hour period.

4. The method of providing an IV nimodipine infusion regimen of claim 3 , wherein 27.6 mg of IV nimodipine provides an equivalent 24-hour plasma nimodipine exposure to 360 mg of oral nimodipine, and provides a similar pulsatile concentration-time profile.

5. The method of providing an IV nimodipine infusion regimen of claim 1 , which can be scaled in direct proportion to a targeted oral dose for a proposed treatment.

6. The method of providing an IV nimodipine infusion regimen of claim 3 , wherein the infusion rate is halved to provide a continuous intravenous nimodipine dose of about 0.075 mg/hour and an intravenous bolus nimodipine dose of about 2 mg administered over about 30 minutes at about 4 hour intervals, to provide equivalent plasma nimodipine exposures as an oral regimen of 30 mg nimodipine administered orally every 4 hours.

7. The method of providing an IV nimodipine infusion regimen of claim 1 , wherein the human has a condition selected from an aneurysm, subarachnoid hemorrhage, vasospastic angina, Prinzmetal angina, stable angina, acute myocardial infarction, myocardial arrest, arrhythmia, systemic hypertension, pulmonary hypertension, congestive heart failure, coronary artery surgery and hypertrophic cardiomyopathy.

8. The method of providing an IV nimodipine infusion regimen of claim 1 , comprising administering the continuous intravenous nimodipine infusion over a period of about three weeks.

9. The method of claim 2 , which provides an IV/oral ratio (%) and its corresponding 90% CI (range) a Day 1 C max of about 92% (82-104); an AUC Day 3, 0-24 hr of about 106% (99-114) and a Day 3 C max : 92% (85-101).

10. The method of claim 1 of providing an IV nimodipine infusion regimen in a human, comprising administering an intravenous bolus infusion of about 3.6 mg nimodipine over about 30 minutes, followed by a continuous intravenous nimodipine infusion of about 1.2 mg/hour for up to 21 days for the treatment of subarachnoid hemorrhage.

11. The method of claim 1 of providing an IV nimodipine infusion regimen in a human, comprising administering an intravenous bolus infusion of about 4.5 mg nimodipine over about 39 minutes, followed by a continuous intravenous nimodipine infusion of about 1.2 mg/hour, wherein the human is a healthy volunteer.

12. The method of claim 1 , wherein the continuous intravenous nimodipine infusion is at a rate from about 0.05 mg/hour to about 1.5 mg/hour and is supplemented with an intravenous bolus administration of nimodipine at the set interval over the 24 hour period, the intravenous bolus administration being from about 1 mg to about 8 mg nimodipine administered intravenously over a time period from about 20 minutes to about 50 minutes.

13. A method of providing an IV nimodipine infusion regimen in human patients, comprising intravenously administering over 24 hours (i) a continuous intravenous nimodipine infusion at a rate from about 0.05 mg/hour to about 1.5 mg/hour over 24 hours supplemented with (ii) intravenous bolus administrations of nimodipine at a set interval over the 24 hours, wherein the human has a condition selected from an aneurysm, subarachnoid hemorrhage, vasospastic angina, Prinzmetal angina, stable angina, acute myocardial infarction, myocardial arrest, arrhythmia, systemic hypertension, pulmonary hypertension, congestive heart failure, coronary artery surgery and hypertrophic cardiomyopathy.

14. The method of claim 13 , wherein the 24-hour AUC and C max of nimodipine provided by the IV nimodipine infusion regimen is equivalent to the 24-hour AUC and C max of 30 mg or 60 mg nimodipine administered orally every 4 hours over 24 hours.

15. The method of claim 13 , wherein the IV nimodipine infusion regimen in human patients is selected from the group consisting of (i) an intravenous bolus nimodipine dose of about 4.15 mg administered over about 30 minutes followed by continuous intravenous nimodipine dose of about 0.15 mg/hour for 3.5 hours, with the sequence repeated as many times as needed; (ii) a continuous intravenous nimodipine dose of about 0.075 mg/hour and an intravenous bolus nimodipine dose of about 2 mg administered over about 30 minutes at about 4 hour intervals, with the sequence repeated as many times as needed; and (iii) an intravenous bolus infusion of about 3.6 mg nimodipine over about 30 minutes, followed by a continuous intravenous nimodipine infusion of about 1.2 mg/hour for up to 21 days.

16. The method of claim 1 , wherein the IV nimodipine infusion regimen is administered via an infusion pump.

17. The method of claim 13 , wherein the IV nimodipine infusion regimen is administered via an infusion pump.

18. A method of providing an IV nimodipine infusion regimen in a human, comprising administering (i) a continuous intravenous nimodipine infusion over at least a 24-hour period supplemented with (ii) intravenous bolus administrations of nimodipine at a set interval over the at least a 24-hour period, wherein the 24-hour C max of the IV nimodipine infusion regimen is 63.086 ng/ml and the 24-hour AUC of the IV nimodipine infusion regimen is 491.630 h*ng/ml.

Assignments (2)

Continuity (2)

References Cited (36)