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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Pharmacokinetics and bioavailability of 5-ethyl-2'-deoxyuridine and its novel (5R,6R)-5-bromo-6-ethoxy-5,6-dihydro prodrugs in mice.

The pharmacokinetics and oral (po) bioavailability of 5-ethyl-2'-deoxyuridine (EDU) and its novel 5,6-dihydro prodrugs (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxyuridine (BEEDU) and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5,6-dihydro-5'-O-valeryl-2'- deoxyuridine (VBEEDU) were determined in male Balb/C mice following intravenous and no administration of a 0.4 mmol/kg dose. EDU was eliminated from blood with a half-life of 35.2 +/- 4.2 min. The mean residence time (MRT) and the area under the blood vs. time curve (AUC) for EDU after iv injection were 45.1 +/- 11.7 min and 1.7 +/- 0.2 mumol.g-1.min, respectively. EDU showed a 49% bioavailability in male.Balb/C mice. The pharmacokinetic parameters and bioavailability of EDU were improved significantly upon administration of the 5,6-dihydro prodrugs BEEDU or VBEEDU. The AUC of EDU after a 0.4 mmol/kg iv dose of BEEDU was 2.1 +/- 0.3 mumol.g-1.min, which is substantially higher than that after iv injection of EDU. The half-life and MRT of EDU were increased to 251.9 +/- 30.2 min and 352.0 +/- 91.5 min, respectively, after injection of BEEDU. The po bioavailability of EDU, after administration of BEEDU, was increased almost 2-fold (81%), compared with that of EDU (49%). The AUC of EDU after iv injection of VBEEDU was 1.8 +/- 0.2 mumol.g-1.min. The half-life and MRT of EDU, the active metabolite of VBEEDU, were 106.0 +/- 23.2 min and 157.0 +/- 40.8 min, which are substantially higher than those for EDU after administration of EDU.(ABSTRACT TRUNCATED AT 250 WORDS)[1]

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