Non-steroidal anti-inflammatory drug dosing regimen

Abstract

A method of administering non-steroidal-anti-inflammatory drugs, in particular propionic acid derivatives such as ibuprofen, or acetaminophen is provided. This method provides improved therapeutic effect, in particular pain relief, over extended time periods.

We claim:  
     
         1 . A method of administering a non-steroidal anti-inflammatory drug, which consists of providing to a mammal an initial dose of said non-steroidal anti-inflammatory drug followed by a second dose of said non-steroidal anti-inflammatory drug about 3 to 5 hours after administration of said initial dose, said non-steroidal anti-inflammatory drug having a duration of therapeutic effect which lasts at least about 6 hours after administration of said second dose.  
     
     
         2 . The method of  claim 1 , wherein said initial dose is at least about twice said second dose.  
     
     
         3 . The method of  claim 2 , wherein said initial dose is about 5 mg/kg to about 12 mg/kg and said second dose is about 2.9 mg/kg to about 6 mg/kg.  
     
     
         4 . The method of  claim 1 , wherein said second dose is administered about 4 hours after said initial dose.  
     
     
         5 . The method of  claim 1 , wherein said non-steroidal anti-inflammatory drug is a propionic acid derivative.  
     
     
         6 . The method of  claim 5 , wherein said propionic acid derivative is selected from the group consisting of ibuprofen, naproxen, benoxaprofen, naproxen sodium, flurbiprofen, fenoprofen, fenbuprofen, ketoprofen, indoprofen, pirprofen, carpofen, oxaprofen, pranoprofen, microprofen, tioxaprofen, suproprofen, alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid.  
     
     
         7 . The method of  claim 6 , wherein said propionic acid derivative is ibuprofen.  
     
     
         8 . The method of  claim 1 , wherein said initial dose and said second dose are administered to the mammal in separate dosage forms.  
     
     
         9 . The method of  claim 1 , wherein said initial dose and said second dose are administered to the mammal in a single dosage form.  
     
     
         10 . The method of  claim 9 , wherein said single dosage form comprises an immediate release portion containing said initial dose of non-steroidal anti-inflammatory drug and a delayed burst release portion containing said second dose of non-steroidal anti-inflammatory drug.  
     
     
         11 . The method of  claim 9 , wherein said single dosage form is a solid dosage form.  
     
     
         12 . The method of  claim 1 , wherein said therapeutic effect is pain relief.  
     
     
         13 . A method of administering a propionic acid derivative to a mammal, over a 12-hour time period, which comprises providing a first peak plasma concentration of said propionic acid derivative of about 25 to about 30 mcg/mL in said mammal about 30 to about 120 minutes after said initial dose, and a second peak plasma concentration of said propionic acid derivative of about 15 to about 30 mcg/mL about 4.5 to about 5.5 hours after administration of said initial dose.  
     
     
         14 . The method of  claim 13 , wherein the plasma concentration in said mammal at about 10 hours after administration of the initial dose is less than about 10 mcg/mL.  
     
     
         15 . A method of administering a propionic acid derivative, which comprises providing to a mammal, over a 12 hour time period, an initial dose of said propionic acid derivative at the beginning of said 12 hour time period, followed by a second dose of said propionic acid derivative about 3 to 5 hours after administration of said initial dose, wherein said initial dose is at least about twice said second dose and no further propionic acid derivative is provided during said 12 hour time period.  
     
     
         16 . The method of  claim 15 , wherein said propionic acid derivative is ibuprofen.  
     
     
         17 . The method of  claim 15 , wherein said initial dose is about 400 mg and said second dose is about 200 mg.  
     
     
         18 . A dosage form comprising an immediate release portion containing an initial dose of a non-steroidal anti-inflammatory drug and a delayed burst release portion containing a second dose of said non-steroidal anti-inflammatory drug, said initial dose being at least about twice said second dose.  
     
     
         19 . The dosage form of  claim 18 , wherein said non-steroidal anti-inflammatory drug is a propionic acid derivative.  
     
     
         20 . The dosage form of  claim 18 , wherein said propionic acid derivative is selected from the group consisting of ibuprofen, naproxen, benoxaprofen, naproxen sodium, flurbiprofen, fenoprofen, fenbuprofen, ketoprofen, indoprofen, pirprofen, carpofen, oxaprofen, pranoprofen, microprofen, tioxaprofen, suproprofen, alminoprofen, tiaprofenic acid, fluprofen and bucloxic acid.  
     
     
         21 . The dosage form of  claim 20 , wherein said propionic acid derivative is ibuprofen.  
     
     
         22 . The dosage form of  claim 18 , wherein said dosage form is a solid dosage form.  
     
     
         23 . The dosage form of  claim 18 , wherein said initial dose is about 5 to about 12 mg/kg and said second dose is about 2.9 to about 6 mg/kg.  
     
     
         24 . A method of administering acetaminophen, which consists of providing to a mammal an initial dose of acetaminophen followed by a second dose of acetaminophen about 3 to 5 hours after administration of said initial dose, said acetaminophen having a duration of therapeutic effect which lasts at least about 6 hours after administration of said second dose.  
     
     
         25 . The method of  claim 24 , wherein said second dose is at least about twice said first dose.  
     
     
         26 . The method of  claim 24 , wherein said second dose is administered about 4 hours after said initial dose.  
     
     
         27 . The method of  claim 24 , wherein said initial dose and said second dose are administered to the mammal in separate dosage forms.  
     
     
         28 . The method of  claim 24 , wherein said initial dose and said second dose are administered to the mammal in a single dosage form.  
     
     
         29 . The method of  claim 28 , wherein said single dosage form comprises an immediate release portion containing said initial dose of acetaminophen and a delayed burst release portion containing said second dose of acetaminophen.  
     
     
         30 . The method of  claim 28 , wherein said single dosage form is a solid dosage form.  
     
     
         31 . The method of  claim 24 , wherein said therapeutic effect is pain relief.  
     
     
         32 . A method of administering acetaminophen, which comprises providing to a mammal, over a 12 hour time period, an initial dose of acetaminophen at the beginning of said 12 hour time period, followed by a second dose of acetaminophen about 3 to 5 hours after administration of said initial dose, wherein said initial dose is at least about twice said second dose and no further acetaminophen is provided during said 12 hour time period.  
     
     
         33 . A dosage form comprising an immediate release portion containing an initial dose of acetaminophen and a delayed burst release portion containing a second dose of acetaminophen, said initial dose being at least about twice said second dose.  
     
     
         34 . The dosage form of  claim 33 , wherein said dosage form is a solid dosage form.  
     
     
         35 . A method of reducing drug exposure of a mammal to an NSAID comprising providing said NSAID to said mammal using the method of  claim 1  or  claim 13 .  
     
     
         36 . A method of administering a therapeutic agent, which consists of providing to a mammal an initial dose of a non-steroidal anti-inflammatory drug followed by a second dose of acetaminophen about 3 to 5 hours after administration of said initial dose of non-steroidal anti-inflammatory drug; said non-steroidal anti-inflammatory drug and acetaminophen having a combined duration of therapeutic analgesic effect which lasts at least about 6 hours after administration of said second dose of acetaminophen.