Method and Composition for the Treatment of Opioid Induced Constipation

摘要

The invention relates to a method of treatment using a solid oral pharmaceutical dosage form comprising an opioid receptor antagonist for use in the treatment of opioid induced constipation comprising the opioid antagonist equivalent to 24 mg of naloxone hydrochloride as twice daily formulation or equivalent to 48 mg of naloxone hydrochloride as once daily formulation, characterized in that the opioid antagonist has a rapid first pass metabolism with a plasma half-life of 2 hours or less in humans within the first 3 hours of oral administration of a solution, wherein the steady state pharmacokinetics result in a constant level of naloxone in the bloodstream, wherein the pharmacokinetics are independent of whether the dosage is administered once or twice daily, wherein the oral dosage form releases the opioid antagonist in a prolonged manner, wherein the in vitro release rate of the opioid antagonist measured using the paddle stirrer method according to Ph. Eur. at 75 rpm in 1000 ml 0.1 N hydrochloric acid at 37° C., is 15%±5% in 1 h, is 26%±5% in 3 h, is 40%±5% in 6 h, is 55%±7% in 10 h, is 67%±8% in 15 h, and is 78%±10% in 20 h.

主权项

1. Method for the treatment of a patient suffering from opioid induced constipation, the method comprising, administering an oral dosage form comprising an opioid receptor antagonist equivalent to 24 mg of naloxone hydrochloride twice daily or equivalent to 48 mg of naloxone hydrochloride once daily, characterized in that the opioid receptor antagonist has a rapid first pass metabolism with a plasma half-life of 2 hours or less in humans within the first 3 hours of oral administration as a solution, wherein the steady state pharmacokinetics of the oral dosage form result in a constant level of opioid receptor antagonist in the bloodstream, wherein the pharmacokinetics of the oral dosage form are independent of whether the dosage is administered once or twice daily, wherein the oral dosage form releases the opioid antagonist in a prolonged manner, wherein the amount of opioid antagonist released measured using the paddle stirrer method according to Ph. Eur. at 75 rpm in 1000 ml 0.1 N hydrochloric acid at 37° C., is 15%±5% in 1 h, is 26%±5% in 3 h, is 40%±5% in 6 h, is 55%±7% in 10 h, is 67%±8% in 15 h, and is 78%±10% in 20 h.