Method of treating pain by administering 24 hour oral opioid formulations exhibiting rapid rate of initial rise of plasma drug level

Abstract

Patients are treated with 24-hour oral sustained release opioid formulations which, upon administrations, provide an initially rapid opioid absorption such that the minimum effective analgesic concentration of the opioid is more quickly achieved. These sustained release opioid formulations include an effective amount of at least one retardant material to cause said opioid analgesic to be released at a such a rate as to provide an analgesic effect after oral administration to a human patient for at least about 24 hours, and are characterized by providing an absorption half-life from 1 to about 8 hours. A method of titrating a human patient utilizing these sustained release opioid formulations is also disclosed.

1 . An oral sustained release opioid formulation comprising: 
 (a) an effective amount of an opioid analgesic, and    (b) an effective amount of at least one retardant material to cause said opioid analgesic to be released at an effective rate to provide an analgesic effect after oral administration to a human patient for at least about 12 hours.    
   
   
       2 - 4 . (canceled)  
   
   
       5 . The sustained release formulation of  claim 1 , wherein said opioid analgesic is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacyl morphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tramadol, tilidine, salts thereof and mixtures thereof.  
   
   
       6 - 26 . (canceled)  
   
   
       27 . The sustained release formulation of  claim 1 , wherein said opioid analgesic is oxymorphone.  
   
   
       28 . The sustained release formulation of  claim 1 , wherein the retardant material comprises a sustained release coating or a sustained release matrix.  
   
   
       29 . The sustained release formulation of  claim 1 , wherein said formulation provides a maximum blood plasma concentration of the opioid analgesic, or of a metabolite thereof, after oral administration to the human patient, which maximum blood plasma concentration: 
 (i) provides a susbstantially equivalent therapeutic effect as 2-14 ng/ml morphine based on a 30 mg dose of morphine sulfate; and    (ii) is less than about four times a blood plasma concentration of the opioid analgesic, or of a metabolite thereof, at about 12 hours after administration.    
   
   
       30 . The sustained release formulation of  claim 29 , wherein the opioid analgsic is oxymorphone.  
   
   
       31 . The sustained release formulation of  claim 29 , wherein the maximum blood plasma concentration provides a substantially equivalent therapeutic effect as 3-8 ng/ml based on a 30 mg dose of morphine sulfate.  
   
   
       32 . The sustained release formulation of  claim 29 , wherein the blood concentration of the opioid analgesic, or of a metabolite thereof, at about 12 hours after oral administration to the human patient is at least a minimally effective analgesic concentration.  
   
   
       33 . The sustained release formulation of  claim 1 , wherein said formulation provides a blood plasma concentration of the opioid analgesic, or of a metabolite thereof, at about 12 hours after oral administration to the human patient, which blood plasma concentration: 
 (i) is at least a minimally effective analgesic concentration for the opioid analgesic; and    (ii) is at least about 25% of a maximum blood concentration of the opioid analgesic, or of a metabolite thereof, after oral administration to the human patient.    
   
   
       34 . The sustained release formulation of  claim 33 , wherein the opioid analgesic is oxymorphone.  
   
   
       35 . The sustained release formulation of  claim 33 , wherein the blood plasma concentration is provided after oral administration of a single dose to the human patient.  
   
   
       36 . The sustained release formulation of  claim 33 , wherein the blood plasma concentration is provided upon repeated oral administration of said formulation to the human patient through steady state conditions.  
   
   
       37 . The sustained release formulation of  claim 33 , wherein the maximum blood plasma concentration provides a substantially equivalent therapeutic effect as 2-14 ng/ml morphine based on a 30 mg dose of morphine sulfate.  
   
   
       38 . The sustained release formulation of  claim 35 , wherein the maximum blood concentration provides a substantially equivalent therapeutic effect as 3-8 ng/ml morphine based on a 30 mg dose of morphine sulfate.  
   
   
       39 . A method of treating a patient for pain, which method comprises orally administering to the patient a formulation which comprises an effective amount of an opioid analgesic, 
 wherein said formulation provides analgesia to a patient for at least about 12 hours after administration.    
   
   
       40 . The method of  claim 39 , wherein said opioid analgesic is selected from the group consisting of alfentanil, allylprodine, alphaprodine, anileridine, benzylmorphine, bezitramide, buprenorphine, butorphanol, clonitazene, codeine, cyclazocine, desomorphine, dextromoramide, dezocine, diampromide, dihydrocodeine, dihydromorphine, dimenoxadol, dimepheptanol, dimethylthiambutene, dioxaphetyl butyrate, dipipanone, eptazocine, ethoheptazine, ethylmethylthiambutene, ethylmorphine, etonitazene fentanyl, heroin, hydrocodone, hydromorphone, hydroxypethidine, isomethadone, ketobemidone, levallorphan, levorphanol, levophenacyl morphan, lofentanil, meperidine, meptazinol, metazocine, methadone, metopon, morphine, myrophine, nalbuphine, narceine, nicomorphine, norlevorphanol, normethadone, nalorphine, normorphine, norpipanone, opium, oxycodone, oxymorphone, papaveretum, pentazocine, phenadoxone, phenomorphan, phenazocine, phenoperidine, piminodine, piritramide, propheptazine, promedol, properidine, propiram, propoxyphene, sufentanil, tram adol, tilidine, salts thereof and mixtures thereof.  
   
   
       41 . The method of  claim 39 , wherein said opioid analgesic is oxymorphone.  
   
   
       42 . The method of  claim 39 , wherein said oral administration provides a maximum blood concentration of the opioid analgesic, or of a metabolite thereof, which maximum blood plasma concentration: 
 (i) provides a substantially equivalent effect as 2-14 ng/ml morphine based on a 30 mg dose of morphine sulfate; and    (ii) is less than about four times a blood plasma concentration of the opioid analgesic, or of a metabolite thereof, at about 12 hours after administration.    
   
   
       43 . The method of  claim 42  wherein the opioid analgesic is oxymorphone.  
   
   
       44 . The method of  claim 39 , 
 which formulation provides a blood plasma concentration of the opioid analgesic, or of a metabolite thereof, at about 12 hours after said administration, which blood plasma concentration is at least a minimally effective analgesic concentration for the opioid analgesic; and    wherein a maximum blood concentration of the opioid analgesic, or of a metabolite thereof, is less than about four times said blood plasma concentration at about 12 hours after oral administration to the human patient.    
   
   
       45 . The method of  claim 44  wherein the opioid analgesic is oxymorphone.