This invention is in the field of chemical restructuring of antimetabolite agents known to have poor oral bioavailability and to cause tissue toxicity as a side effect by producing their orotate derivatives. More particularly it concerns orotate derivatives of the methotrexate and trimetrexate that are found to improve the oral bioavailability and clearance compared with their respective forms- methotrexate and trimetrexate currently in use. The present invention provides methotrexate orotate ha...

This invention is in the field of chemical restructuring of antimetabolite agents known to have poor oral bioavailability and to cause tissue toxicity as a side effect by producing their orotate derivatives.More particularly it concerns orotate derivatives of the methotrexate and trimetrexate that are found to improve the oral bioavailability and clearance compared with their respective forms-methotrexate and trimetrexate currently in use.The present invention provides methotrexate orotate havin...

This invention is in the field of chemical restructuring of antimetabolite agents known to have poor oral bioavailability and to cause tissue toxicity as a side effect by producing their orotate derivatives. More particularly it concerns orotate derivatives of the methotrexate and trimetrexate that are found to improve the oral bioavailability and clearance compared with their respective forms—methotrexate and trimetrexate currently in use. The present invention provides methotrexate orot...

The present invention provides for a crystalline form of trimetrexate either as a glucuronate acetate hydrochloride methanosulfonate or lactate salt which can be processed galenically as a stable well-define d solid substance and processes for producing the crystalline forms. Such crystalline forms allow for prolonged stability in storage and f or oral and intravenous administration of the drug.

Combinations of (a) taxol taxotere or their derivatives with (b) a therapeutic substance are used in the treatment of neoplastic disorders.Pref. (b) is an alkylating agent (esp. cyclophosphamide ifosamide melphalan hexamethyl melamine thiotepa and dacarbazine) an anti-metabolite (esp. 5-fluorouracil cytarabin methotrexate idatrexate and trimetrexate) a fusel poison (esp. a vinca alkaloid their synthetic and semi-synthetic analogues estramustine and taxoids) an epidophyllotoxin (esp. etoposide or...

This invention is in the field of chemical restructuring of antimetabolite agents known to have poor oral bioavailability and to cause tissue toxicity as a side effect by producing their orotate derivatives. More particularly it concerns orotate derivatives of the methotrexate and trimetrexate that are found to improve the oral bioavailability and clearance compared with their respective forms- methotrexate and trimetrexate currently in use. The present invention provides methotrexate orotate ha...

This invention is directed to the novel composition of matter trimetrexate ascorbate to compositions comprising trimetrexate ascorbate and to compositions comprising trimetrexate and ascorbic acid. These compositions are useful in the treatment of diseases in mammals such as but not limited to cancer bacterial and protozoal infections malaria psoriasis and rheumatoid arthritis. The invention is further related to methods of stabilizing trimetrexate to degradation caused by heat light oxygen or w...