Compositions and methods using a cannabinoid to enhance bioavailability of a statin
The invention relates to pharmaceutical compositions comprising a statin and a cannabinoid, and their use for the treatment of hypercholesterolemia and atherosclerosis. It has been found that compositions combining a statin and a cannabinoid are improved over existing statin formulations. The compositions of the invention for example allow for a lower effective dose of statin and a reduction of the adverse effects seen with statins taken alone. Dosing ranges and formulations suitable for oral, buccal, and sublingual administration are disclosed. Various specific cannabinoids such as cannabidiol and synthetic cannabidiols selected for their anti-inflammatory, antioxidant, and anti-atherosclerotic effect are shown to be particularly advantageous.
1. A pharmaceutical composition for once daily dosing, useful in enhancing the bioavailability upon oral administration to a human patient of a statin, comprising:
(a) a reduced daily dosage amount of the statin; and
(b) a phytocannabinoid;
wherein the pharmaceutical composition is formulated for oral administration, and wherein the reduced daily dosage amount of the statin is less than the standard daily dosage amount for the statin when taken alone.
2. The pharmaceutical composition of claim 1 wherein the phytocannabinoid is selected from the group consisting of tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabinodiol or cannabidinodiol (CBDL or CBND), cannabichromene (CBC), cannabielsoin (CBE), cannabicyclol (CBL), cannabicitran (CBT), cannabivarin (CBV), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), and cannabigerol monomethyl ether (CBGM).
3. The pharmaceutical composition of claim 1 wherein the phytocannabinoid is CBD.
4. The pharmaceutical composition of claim 1 wherein the statin and the phytocannabinoid are both substrates of a CYP enzyme.
5. The pharmaceutical composition of claim 4 wherein the CYP enzyme is CYP3A4.
6. The pharmaceutical composition of claim 5 wherein the statin is atorvastatin, lovastatin, or simvastatin.
7. The pharmaceutical composition of claim 4 wherein the CYP enzyme is CYP2C9.
8. The pharmaceutical composition of claim 7 wherein the statin is fluvastatin, pitavastatin, or rosuvastatin.
9. The pharmaceutical composition of claim 4 wherein the CYP enzyme is CYP2C19.
10. The pharmaceutical composition of claim 9 wherein the statin is rosuvastatin.
11. A method of enhancing the bioavailability upon oral administration to a human patient of a statin, comprising orally co-administering to the human patient the statin in a reduced daily dosage amount and a phytocannabinoid, and wherein the reduced daily dosage amount of the statin is less than the standard daily dosage amount for the statin when taken alone.
12. The method of claim 11 wherein the phytocannabinoid is selected from the group consisting of tetrahydrocannabinol (THC), cannabidiol (CBD), cannabinol (CBN), cannabigerol (CBG), cannabinodiol or cannabidinodiol (CBDL or CBND), cannabichromene (CBC), cannabielsoin (CBE), cannabicyclol (CBL), cannabicitran (CBT), cannabivarin (CBV), cannabidivarin (CBDV), tetrahydrocannabivarin (THCV), cannabichromevarin (CBCV), cannabigerovarin (CBGV), and cannabigerol monomethyl ether (CBGM).
13. The method of claim 11 wherein the phytocannabinoid is CBD.
14. The method of claim 11 wherein the statin and the phytocannabinoid are both substrates of a CYP enzyme.
15. The method of claim 14 wherein the CYP enzyme is CYP3A4.
16. The method of claim 15 wherein the statin is atorvastatin, lovastatin, or simvastatin.
17. The method of claim 14 wherein the CYP enzyme is CYP2C9.
18. The method of claim 17 wherein the statin is fluvastatin, pitavastatin, or rosuvastatin.
19. The method of claim 14 wherein the CYP enzyme is CYP2C19.
20. The method of claim 19 wherein the statin is rosuvastatin.