Method of increasing drug oral bioavailability and compositions of less toxic orotate salts

A method of making an orotate salt of a pharmaceutical agent, said pharmaceutical agent selected from the group of consisting of acetanilide, adriamycin, aminoacridine, aminoimidazole, aminoquinoline, anilide, anthracycline antibiotic, antestrogen, benzazepine, benzhydryl compound, bezodiazpine, benzofuran, cannabinoid, cephalosporine, colchicines, cyclic peptide, cyclophosphamide, dibenzazepine, digitalis glycoside, dihydropyridine, doxorubicin, epiphodophyllotoxin, epirubicin, ergeline, ergot alkaloid, fluorouracil, imidazole, isoquinoline, macrolide, methotrexate, naphthalene, nitrogen mustard, opioid, oxazune, oxazole, paclitaxel, phenothiazine, phenylalkamine, phenylpiperidine, piperazine, piperidine, polycyclic aromatic hydrocarbon, pyridine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, quinazoline, quinoline, quinine, rauwolfa aalkaloid, retinoid, salicylate, steroid, stilbene, sulfone, sulfonylurea, tamoxifen, taxol, taxotere, triazole, tropane, vinblastine or vinca alkaloid and said method comprising:

• a) dissolving the pharmaceutical agent and orotic acid in N,N-dimethy acetamide and boiling the mixture;
• and
• b) cooling and drying the mixture to obtain the precipitate of the orotate salt of the pharmaceutical agent.

A method of increasing the clearance of a pharmaceutical agent by converting said pharmaceutical agent to an orotate salt composition and, administering said orotate salt to a subject in need thereof, said pharmaceutical agent selected from the group of consisting of acetanilide, adriamycin, aminoacridine, aminoimidazole, aminoquinoline, anilide, anthracycline antibiotic, antestrogen, benzazepine, benzhydryl compound, bezodiazpine, benzofuran, cannabinoid, cephalosporine, colchicines, cyclic peptide, cyclophosphamide, dibenzazepine, digitalis glycoside, dihydropyridine, doxorubicin, epiphodophyllotoxin, epirubicin, ergeline, ergot alkaloid, fluorouracil, imidazole, isoquinoline, macro lide, methotrexate, naphthalene, nitrogen mustard, opioid, oxazune, oxazole, paclitaxel, phenothiazine, phenylalkamine, phenylpiperidine, piperazine, piperidine, polycyclic aromatic hydrocarbon, pyridine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, quinazoline, quinoline, quinine, rauwolfa aalkaloid, retinoid, salicylate, steroid, stilbene, sulfone, sulfonylurea, tamoxifen, taxol, taxotere, triazole, tropane, vinblastine or vinca alkaloid.

A method of reducing toxicity of a pharmaceutical agent by converting said pharmaceutical agent to an orotate salt composition and, administering said orotate salt to a subject in need thereof, said pharmaceutical agent selected from the group of consisting of acetanilide, adriamycin, aminoacridine, aminoimidazole, aminoquinoline, anilide, anthracycline antibiotic, antestrogen, benzazepine, benzhydryl compound, bezodiazpine, benzofuran, cannabinoid, cephalosporine, colchicines, cyclic peptide, cyclophosphamide, dibenzazepine, digitalis glycoside, dihydropyridine, doxorubicin, epiphodophyllotoxin, epirubicin, ergeline, ergot alkaloid, fluorouracil, imidazole, isoquinoline, macrolide, methotrexate, naphthalene, nitrogen mustard, opioid, oxazune, oxazole, paclitaxel, phenothiazine, phenylalkamine, phenylpiperidine, piperazine, piperidine, polycyclic aromatic hydrocarbon, pyridine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, quinazoline, quinoline, quinine, rauwolfa aalkaloid, retinoid, salicylate, steroid, stilbene, sulfone, sulfonylurea, tamoxifen, taxol, taxotere, triazole, tropane, vinblastine or vinca alkaloid.

A method of increasing the effectiveness of a pharmaceutical agent by converting said pharmaceutical agent to an orotate salt composition and, administering said orotate salt to a subject in need thereof, said pharmaceutical agent selected from the group of consisting of acetanilide, adriamycin, aminoacridine, aminoimidazole, aminoquinoline, anilide, anthracycline antibiotic, antestrogen, benzazepine, benzhydryl compound, bezodiazpine, benzofuran, cannabinoid, cephalosporine, colchicines, cyclic peptide, cyclophosphamide, dibenzazepine, digitalis glycoside, dihydropyridine, doxorubicin, epiphodophyllotoxin, epirubicin, ergeline, ergot alkaloid, fluorouracil, imidazole, isoquinoline, macrolide, methotrexate, naphthalene, nitrogen mustard, opioid, oxazune, oxazole, paclitaxel, phenothiazine, phenylalkamine, phenylpiperidine, piperazine, piperidine, polycyclic aromatic hydrocarbon, pyridine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, quinazoline, quinoline, quinine, rauwolfa aalkaloid, retinoid, salicylate, steroid, stilbene, sulfone, sulfonylurea, tamoxifen, taxol, taxotere, triazole, tropane, vinblastine or vinca alkaloid.

A composition comprising an orotate salt of a pharmaceutical agent, said pharmaceutical agent selected from the group consisting of:

• acetanilide, adriamycin, aminoacridine, aminoimidazole, aminoquinoline, anilide, anthracycline antibiotic, antestrogen, benzazepine, benzhydryl compound, bezodiazpine, benzofuran, cannabinoid, cephalosporine, colchicines, cyclic peptide, cyclophosphamide, dibenzazepine, digitalis glycoside, dihydropyridine, doxorubicin, epiphodophyllotoxin, epirubicin, ergeline, ergot alkaloid, fluorouracil, imidazole, isoquinoline, macrolide, methotrexate, naphthalene, nitrogen mustard, opioid, oxazune, oxazole, paclitaxel, phenothiazine, phenylalkamine, phenylpiperidine, piperazine, piperidine, polycyclic aromatic hydrocarbon, pyridine, pyridine, pyrimidine, pyrrolidine, pyrrolidinone, quinazoline, quinoline, quinine, rauwolfa aalkaloid, retinoid, salicylate, steroid, stilbene, sulfone, sulfonylurea, tamoxifen, taxol, taxotere, triazole, tropane, vinblastine or vinca alkaloid.