Development of a Prodrug of Levofloxacin to Avoid Chelation with Al3+ and of Pemetrexed Dimedoxomil Esters for Oral Administration

Kenji Matsuyama
2017 Yakugaku zasshi  
An ethoxycarbonyl 1-ethyl hemiacetal ester of levo‰oxacin (LVFX-EHE) avoids insoluble chelate formation with metal-containing drugs in the intestinal tract and is rapidly hydrolyzed to the parent drug. Furthermore, the minimum inhibitory concentration conˆrms that LVFX-EHE is less likely to cause pseudomembranous colitis because of less susceptibility to normal intestinal bacteria ‰ora. Pemetrexed dimedoxomil, the prodrug of pemetrexed, was synthesized via reaction with medoxomil bromide after
more » ... omil bromide after modiˆcation of L-glutamate with the tert-butyloxycarbonyl protecting group (BOC), followed by hydrolysis of the BOC moiety with tri‰uoroacetic acid (TFA) in CH 2 Cl 2 at a temperature of 0°C for 2 h. A serum pemetrexed concentration of >2 mg/mL was observed after oral administration of pemetrexed dimedoxomil at a dose of 60 mg/kg to rats.
doi:10.1248/yakushi.17-00095 pmid:28867695 fatcat:4bis7tcojzaftnqwmlutsuxzxq