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An ethoxycarbonyl 1-ethyl hemiacetal ester of levofloxacin (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 confirms that LVFX-EHE is less likely to cause pseudomembranous colitis because of less susceptibility to normal intestinal bacteria flora. Pemetrexed dimedoxomil, the prodrug of pemetrexed, was synthesized via reaction with medoxomil bromide after modification of L-glutamate with the tert-butyloxycarbonyl protecting group (BOC), followed by hydrolysis of the BOC moiety with trifluoroacetic acid (TFA) in CH 2 Cl 2 at a temperature of 0°C for 2 h. A serum pemetrexed concentration of &gt;2 μg/mL was observed after oral administration of pemetrexed dimedoxomil at a dose of 60 mg/kg to rats.

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Development of a Prodrug of Levofloxacin to Avoid Chelation with Al&lt;sup&gt;3+&lt;/sup&gt; and of Pemetrexed Dimedoxomil Esters for Oral Administration