This is a comparative pharmacokinetics study of linezolid (Lzd), and two novel\noxazolidinone antibacterial agentsââ?¬â?PH027 and PH051ââ?¬â?in rabbits to determine if the discrepancy\nbetween the in vitro and in vivo activities of the novel compounds is due to pharmacokinetic factors.\nThe pharmacokinetics after IV and oral administration, plasma protein binding and tissue distribution\nfor the three compounds were compared. The elimination half-lives were 52.4 6.3, 68.7 12.1\nand 175 46.1 min for Lzd, PH027 and PH051, respectively. The oral bioavailability for Lzd, PH027\nand PH051 administered as suspension were 38.7%, 22.1% and 4.73%, which increased significantly\nwhen administered as microemulsion to 51.7%, 72.9% and 13.9%. The plasma protein binding were\n32ââ?¬â??34%, 37ââ?¬â??38% and 90ââ?¬â??91% for Lzd, PH027 and PH051. The tissue distribution for PH027 and\nPH051 in all investigated tissues were higher than that for Lzd. It can be concluded that the lower\nbioavailability of PH027 and PH051 compared to Lzd when administered as suspension is the main\ncause of their lower in vivo activity, despite their comparable in vitro activity. Differences in the other\npharmacokinetic characteristics cannot explain the lower in vivo activity. The in vivo activity of the\nnovel compounds should be re-evaluated using formulations with good oral bioavailability.
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