Benzoic acid, benzoic acid derivatives and heteroaryl carboxylic acid conjugates of hydrocodone, prodrugs, methods of making and use thereof
View Patent ↗The presently described technology provides methods of treating a patient having moderate to severe pain, narcotic or opioid abuse or narcotic or opioid withdrawal. The presently described methods are carried out by comprising administering to the patient a pharmaceutically effective amount of a composition comprising acetaminophen and benzoate-hydrocodone hydrochloride. The composition has reduced side effects when compared with unconjugated hydrocodone.
1. A method for treating a patient having moderate to severe pain, narcotic or opioid abuse, or narcotic or opioid withdrawal comprising administering to the patient a pharmaceutically effective amount of a composition comprising acetaminophen and benzoate-hydrocodone hydrochloride wherein the composition has reduced side effects when compared with unconjugated hydrocodone.
2. The method of claim 1 , wherein the composition comprises benzoate-hydrocodone hydrochloride and acetaminophen having a molar ratio from 0.001:1 to 1000:1.
3. The method of claim 1 , wherein the composition is a conjugate.
4. The method of claim 1 , wherein the composition is a prodrug.
5. The method of claim 1 , wherein the composition is used to reduce or prevent oral, intranasal or intravenous drug abuse; or to provide oral, intranasal or parenteral drug abuse resistance.
6. The method of claim 1 , wherein the composition exhibits an improved AUC and rate of release of hydrocodone over time when compared to unconjugated hydrocodone over the same time period; exhibits lower exposure to hydrocodone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.
7. The method of claim 1 , wherein the composition exhibits an improved AUC and rate of release of hydromorphone over time when compared to unconjugated hydrocodone over the same time period; exhibits lower exposure to hydromorphone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.
8. The method of claim 1 , wherein the composition exhibits lower maximum peak exposure (C max ) to hydrocodone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.
9. The method of claim 1 , wherein the composition exhibits lower maximum peak exposure (C max ) to hydromorphone at about more than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.
10. The method of claim 1 , wherein the composition is provided in a dosage form selected from the group consisting of: a tablet, a capsule, a caplet, a suppository, a troche, a lozenge, an oral powder, a solution, an oral film, a thin strip, a slurry, and a suspension.
11. The method of claim 1 , wherein the composition is provided in an amount sufficient to provide a therapeutically bioequivalent AUC for hydrocodone at about lower than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.
12. The method of claim 1 , wherein at least one composition is provided in an amount sufficient to provide a therapeutically bioequivalent AUC and C max for hydrocodone at about lower than 53 mg when compared to an equivalent molar amount of unconjugated hydrocodone.
13. The method of claim 1 , wherein one of the reduced side effects comprises a lower than normal concentration of oxygen in arterial blood of the patient.
14. The method of claim 1 , wherein one of the reduced side effects comprises respiratory depression in the patient.