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

Abstract

A method of increasing the bioavailability upon oral administration of a pharmacologically active target agent, particularly an antitumor or antineoplastic agent which exhibits poor or inconsistent oral bioavailability (e.g., paclitaxel, docetaxel or etoposide), comprises the oral co-administration to a mammalian patient of the target agent and an oral bioavailability-enhancing agent (e.g., cyclosporin A, cyclosporin D, cyclosporin F or ketoconazole). The enhancing agent may be administered orally from 0.5-24 hrs. prior to the oral administration of one or more doses of the target agent, substantially simultaneously with the target agent or both prior to and substantially simultaneously with the target agent. A method of treating mammalian patients suffering from diseases responsive to target agents with poor oral bioavailability, as well as oral dosage forms containing such target agents, combination oral dosage forms containing bioavailability-enhancing agents and target agents and kits containing enhancing and target agent dosage forms and dosing information for the co-administration of the same are also disclosed.

1 . A method of increasing the bioavailability upon oral administration to a human patient of a taxane, comprising orally co-administering to the human patient a taxane and an oral bioavailability-enhancing agent comprising a P-glycoprotein inhibitor, wherein the oral bioavailability enhancing agent is administered substantially simultaneously with administration of the taxane, prior to administration of the taxane, or both prior to and substantially simultaneously with administration of the taxane.