DEVELOPMENT OF A PHYSICAL MODEL FOR SIMULTANEOUS DIFFUSION BIOCONVERSION OF METHOTREXATE DIALKYL ESTERS - A POTENTIAL PARALLEL/SEQUENTIAL METABOLIC SCHEME/

A physical model has been developed which accommodates simultaneous di ffusion/parallel-sequential bioconversion process through hairless mou se skin. The model includes both tape-stripped and full-thickness skin to describe the diffusion/bioconversion of methotrexate (MTX) dialkyl esters, in which a potential parallel/sequential esterase metabolic s cheme is operative. Simulations are also included to illustrate the be havior of MTX dialkyl esters with the simultaneous diffusion/bioconver sion parameters in which the metabolism stops at the level of MTX mono alkyl esters.