Method, compositions and kits for increasing the oral bioavailability of pharmaceutical agents

A method of treating a mammalian patient afflicted with a disease responsive to a pharmacologically active target agent comprising the oral co-administration to the patient of the target agent and an oral bioavailability-enhancing agent selected from the group consisting of cyclosporins A through Z, (Me-Ile-4)-cyclosporin, dihydro cyclosporin A dihydro cyclosporin C, acetyl cyclosporin A, and related oligopeptides produced by species in the genus Topycladium, ketoconazole, dexverapamil, amiodarone, nifedipine, reserpine, quinidine, nicardipine, ethacrynic acid, propafenone, reserpine, amiloride, ergot alkaloids, cefoperazone, tetracycline, chloroquine, fosfomycin, ivermectin, tamoxifen, VX-710, VX-853, genistein and related isoflavonoids, calphostin, ceramides, morphine, morphine congeners, other opioids and opioid antagonists.

A method of treating a mammalian patient suffering from cancer of the liver, gastrointestinal tract, pancreas or lungs or from Kaposi's sarcoma, comprising the oral administration to the patient of an antitumor or antineoplastic target agent in a manner which creates a higher initial local concentration of the target agent in the patient's liver, gastrointestinal tract, pancreas or lungs than the initial concentration in the general systemic circulation or in other organs.

An oral pharmaceutical dosage form containing a pharmacologically active target agent selected from the group consisting of paclitaxel, docetaxel, other taxanes and pharmaceutically acceptable salts and derivatives thereof in an amount effective to treat a paclitaxel-responsive disease upon oral co-administration to a mammalian patient with an oral bioavailability enhancing agent.

An oral pharmaceutical dosage form containing a pharmacologically active target agent selected from the group consisting of etoposide and pharmaceutically acceptable salts and derivatives thereof in an amount effective to treat an etoposide-responsive disease upon oral co-administration to a mammalian patient with an oral bioavailability enhancing agent.

An oral pharmaceutical dosage form containing a pharmacologically active target agent and an oral bioavailability enhancing agent.

A pharmaceutical dosage form comprising an antitumor or antineoplastic agent selected from the group consisting of paclitaxel, docetaxel, other taxanes and pharmaceutically acceptable salts and derivatives thereof, said dosage form being suitable for oral administration to a patient suffering from cancer to provide an effective antitumor or antineoplastic blood and tissue concentration of said agent.

A pharmaceutical kit to be used in the treatment of mammalian patients suffering from a condition responsive to a pharmacologically active agents whose oral bioavailability is increased by the oral co-administration of a bioavailability enhancing agent, said kit comprising an oral dosage form containing an enhancing agent and an oral dosage form containing a target agent, or an oral dosage form containing both an enhancing agent and a target agent.