Accumulation of 5-ethyl-2'-deoxyuridine and its 5,6-dihydro prodrugs in murine lung and its potential clinical application.
The accumulation of 5-ethyl-2'-deoxyuridine (EDU), (--)-trans-(5S,6S)-5-bromo-5-ethyl-6-methoxy-5,6- dihydro-2'-deoxyuridine [(5S,6S)-BMEDU], (+)-trans-(5R,6R) -5-bromo-ethyl-6-methoxy-5,6-dihydro- 2'-deoxyuridine [(5R,6R)-BMEDU], (+)-trans-(5R,6R)-5-bromo- 5-ethyl-6-ethoxy-5,6-dihydro-2'-deoxy- uridine (BEEDU), (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy -5,6-dihydro-5'-O-valeryl-2'deoxyuridine (VBEEDU) [formula: see text] and (+)-trans-(5R,6R)-5-bromo-5-ethyl-6-ethoxy-5, 6-dihydro-3'-5'-di-O-valeryl-2'-deoxyuridine [formula: see text] (DVBEEDU) in lung and other tissues was investigated in male Balb-C mice following intravenous injection of the corresponding 4-(14)C-labelled compounds. EDU showed a rapid distribution into liver and lung immediately after injection, and the overall levels of radioactivity in blood, liver and lung were similar. The distribution of radioactivity in lung after injection of [4-(14)C](5S,6S)-BMEDU and [4-(14)C]5R,6R)-BMEDU were substantially different from one another and also from that of[4(-14)C]EDU. The radioactivity level present in lung samples after injection of both (4-(14C](5S,6S)-BMEDU and [4-(14)C](5R,6R)-BMEDU was substantially higher than that in blood samples. Radioactivity levels present in lung samples taken at 18 min after injection of [4-(14)C]BEEDU were significantly higher (P < 0.05) than those for liver and blood samples. Although the radioactivity present in lung samples after injection of [4-(14)C]BEEDU did not provide a higher radioactivity level in lung samples than did [4-(14)C]BEEDU.(ABSTRACT TRUNCATED AT 250 WORDS)
Cheraghali
A M
AM
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Canada.
Morin
K W
KW
Kumar
R
R
Knaus
E E
EE
Wiebe
L I
LI
D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003857:Deoxyuridine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000998:Antiviral Agents; D011355:Prodrugs; C022811:edoxudin; D003857:Deoxyuridine