PHARMACEUTICAL COMPOSITIONS FOR EXTENDED RELEASE OF OXYCODONE AND ACETAMINOPHEN RESULTING IN A QUICK ONSET AND PROLONGED PERIOD OF ANALGESIA
The present disclosure provides extended release pharmaceutical compositions comprising oxycodone and acetaminophen that produce a quick initial onset of analgesia, yet, maintain analgesia for about 12 hours after administration of the composition to a subject in need thereof. The pharmaceutical compositions disclosed herein also reduce the levels of acetaminophen in a subject's blood near the end of the dosing interval because the acetaminophen released by the pharmaceutical composition is being eliminated by a subject's body faster than it is being absorbed.
1 . A method of treating pain in a human subject comprising:
administering to the subject a pharmaceutical composition comprising oxycodone or a pharmaceutically acceptable salt thereof and acetaminophen,
wherein the total amount of acetaminophen in the composition is about 325 mg to about 650 mg and the total amount of oxycodone or a pharmaceutically acceptable salt thereof in the composition is about 7.5 mg to about 15 mg;
wherein the mean AUC for oxycodone at steady state is about 11.0 ng·hr/mL/mg to about 17.0 ng·hr/mL/mg and the mean AUC for acetaminophen at steady state is about 40.0 ng·hr/mL/mg to about 50.0 ng·hr/mL/mg; and
wherein the subject achieves therapeutic blood levels of both the oxycodone and the acetaminophen within about one hour after administration of the composition and maintains analgesia for at least about 10 hours after administration of the composition.
2 . The method of claim 1 , wherein the mean AUC for oxycodone is about 12.0 ng·hr/mL/mg to about 16.0 ng·hr/mL/mg.
3 . The method of claim 1 , wherein the mean AUC for oxycodone is about 13.0 ng·hr/mL/mg to about 15.0 ng·hr/mL/mg.
4 . The method of claim 1 , wherein the mean AUC for acetaminophen at steady state is about 35.0 ng·hr/mL/mg to about 45.0 ng·hr/mL/mg.
5 . The method of claim 1 , wherein the mean AUC for acetaminophen at steady state is about 37.0 ng·hr/mL/mg to about 42.0 ng·hr/mL/mg.
6 . The method of claim 1 , wherein the subject achieves therapeutic blood levels of the oxycodone within about thirty minutes after administration.
7 . The method of claim 1 , wherein the subject achieves therapeutic blood levels of the acetaminophen within about thirty minutes after administration.
8 . The method of claim 1 , wherein the subject achieves therapeutic blood levels of both the oxycodone and the acetaminophen within about thirty minutes after administration.
9 . The method of claim 1 , wherein the composition comprises about 325 mg of acetaminophen and about 7.5 mg of oxycodone or a pharmaceutically acceptable salt thereof.
10 . The method of claim 1 , wherein the composition comprises about 650 mg of acetaminophen and about 15 mg of oxycodone or a pharmaceutically acceptable salt thereof.
11 . The method of claim 1 , wherein the subject achieves steady state plasma concentrations for oxycodone and acetaminophen within 24 hours of administration of the composition.
12 . The method of claim 1 , wherein the subject achieves steady state plasma concentrations for oxycodone within 24 hours of administration of the composition.
13 . The method of claim 1 , wherein the subject achieves steady state plasma concentrations for acetaminophen within 24 hours of administration of the composition.
14 . The method of claim 1 , wherein the median T max for acetaminophen at steady state is about 0.5 hour to about 1.0 hour.
15 . The method of claim 1 , wherein the median T max for acetaminophen at steady state is about 0.5 hour to about 0.75 hour.
16 . The method of claim 1 , wherein the median T max for oxycodone at steady state is about 1.5 hours to about 3.5 hours.
17 . The method of claim 1 , wherein the median T max for oxycodone is about 2 hours to about 3 hours.
18 . A method of treating pain in a human subject comprising:
administering to the subject a pharmaceutical composition comprising oxycodone or a pharmaceutically acceptable salt thereof and acetaminophen,
wherein the total amount of acetaminophen in the composition is about 325 mg to about 650 mg and the total amount of oxycodone or a pharmaceutically acceptable salt thereof in the composition is about 7.5 mg to about 15 mg;
wherein the median T max for acetaminophen at steady state is about 0.5 hour to about 1.0 hour and the mean C max for acetaminophen at steady state is about 6.0 ng/mL/mg to about 9.0 ng/mL/mg;
wherein the median T max for oxycodone at steady state is about 1.5 hours to about 3.5 hours and the mean C max for oxycodone at steady state is about 1.5 ng/mL/mg to about 2.0 ng/mL/mg; and
wherein the subject achieves therapeutic blood levels of both the oxycodone and the acetaminophen within about one hour after administration of the composition and maintains analgesia for at least about 12 hours after administration of the composition.
19 . The method of claim 18 , wherein the mean C max for acetaminophen at steady state is about 7.0 ng/mL/mg to about 8.0 ng/mL/mg.
20 . The method of claim 18 , wherein the mean C max for oxycodone is about 1.6 ng/mL/mg to about 1.95 ng/mL/mg.