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 having the formula: ##STR00001##