Treatment of poor metabolizers of dextromethorphan with a combination of bupropion and dextromethorphan
Disclosed herein is a method of safely treating a nervous system condition with a combination of dextromethorphan and bupropion. This method is intended for patients having a neurological condition or a psychiatric condition, such as major depressive disorder, and a CYP2D6 poor metabolizer genotype or a CYP2D6 poor metabolizer phenotype.
1. A method of treating major depressive disorder in a CYP2D6 poor metabolizer comprising, selecting a human patient known to be a poor CYP2D6 metabolizer who is experiencing major depressive disorder, and administering, once daily for at least two weeks to the human patient, a dosage form containing 105 mg or less of bupropion hydrochloride, or a molar equivalent amount of the free base or another salt form of bupropion and 45 mg or less of dextromethorphan hydrobromide, or a molar equivalent amount of the free base or another salt form of dextromethorphan.
2. The method of claim 1 , wherein 105 mg of bupropion hydrochloride and 45 mg of dextromethorphan hydrobromide is present in the dosage form.
3. The method of claim 2 , wherein the once-daily administration for 8 days avoids the human patient having an about 3.4-fold increase in AUC 0-12 of dextromethorphan as compared to the AUC 0-12 of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.
4. The method of claim 2 , wherein the once-daily administration for 8 days avoids the human patient having an about 3-fold increase in C max of dextromethorphan as compared to the C max of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.
5. The method of claim 2 , wherein the dosage form is orally administered in the morning.
6. The method of claim 5 , wherein the dextromethorphan is in an immediate-release formulation.
7. The method of claim 6 , wherein the bupropion is in an extended-release formulation.
8. The method of claim 7 , wherein the once-daily administration for 8 days avoids the human patient having an about 3.4-fold increase in AUC 0-12 of dextromethorphan as compared to the AUC 0-12 of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.
9. The method of claim 7 , wherein the once-daily administration for 8 days avoids the human patient having an about 3-fold increase in C max of dextromethorphan as compared to the C max of dextromethorphan that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.
10. The method of claim 7 , wherein the dosage form further contains a carbomer homopolymer.
11. The method of claim 7 , wherein the dosage form further contains colloidal silicon dioxide.
12. The method of claim 7 , wherein the dosage form further contains crospovidone.
13. The method of claim 7 , wherein the dosage form further contains glyceryl monocaprylocaprate.
14. The method of claim 7 , wherein the dosage form further contains L-cysteine hydrochloride monohydrate.
15. The method of claim 7 , wherein the dosage form further contains magnesium stearate.
16. The method of claim 7 , wherein the dosage form further contains microcrystalline cellulose.
17. The method of claim 7 , wherein the dosage form further contains polyvinyl alcohol.
18. The method of claim 7 , wherein the dosage form further contains red iron oxide.
19. The method of claim 7 , wherein the dosage form further contains sodium lauryl sulfate.
20. The method of claim 7 , wherein the dosage form further contains stearic acid.
21. The method of claim 7 , wherein the dosage form further contains talc.
22. The method of claim 7 , wherein the dosage form further contains titanium dioxide.
23. The method of claim 7 , wherein the dosage form further contains yellow iron oxide.
24. The method of claim 8 , wherein twice-daily administration of the solid dosage form to the human patient for 8 days would result in the human patient having about same AUC 0-12 of bupropion as compared to the AUC 0-12 of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.
25. The method of claim 9 , wherein twice-daily administration of the solid dosage form to the human patient for 8 days would result in the human patient having about same C max of bupropion as compared to the C max of bupropion that would result after 8 days of twice daily administration of the dosage form to a human patient who is an extensive or ultra-extensive CYP2D6 metabolizer.
26. A method of treating major depressive disorder in a CYP2D6 poor metabolizer comprising, selecting a human patient known to be a poor CYP2D6 metabolizer who is experiencing major depressive disorder, and administering, once daily for at least four weeks to the human patient, a dosage form containing 105 mg or less of bupropion hydrochloride, or a molar equivalent amount of the free base or another salt form of bupropion and 45 mg or less of dextromethorphan hydrobromide, or a molar equivalent amount of the free base or another salt form of dextromethorphan.
27. The method of claim 26 , wherein the dextromethorphan is in an immediate-release formulation.
28. The method of claim 26 , wherein the bupropion is in an extended-release formulation.
29. The method of claim 26 , wherein the dosage form further contains a carbomer homopolymer.
30. The method of claim 26 , wherein the dosage form further contains colloidal silicon dioxide.