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Effects of water deprivation for 72 hours on the pharmacokinetics of DA‐7867, a new oxazolidinone, in rats
Author(s) -
Bae Soo K.,
Kim Yu C.,
Lee Jae K.,
Kwon Jong W.,
Yoo Moohi,
Lee Inchul,
Lee Myung G.
Publication year - 2006
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.496
Subject(s) - dehydration , pharmacokinetics , chemistry , oral administration , gastrointestinal tract , urine , medicine , endocrinology , pharmacology , biochemistry
The pharmacokinetic parameters of DA‐7867 were compared after intravenous and oral administration at a dose of 10 mg/kg in control rats and in rats with water deprivation for 72 h (rat model of dehydration). After intravenous administration in the rat model of dehydration, the Cl nr (0.654 versus 0.992 ml/min/kg) and Cl r (0.0273 versus 0.0784 ml/min/kg) values were significantly slower than in the controls. The slower Cl nr could be due mainly to a significantly smaller total amount of unchanged DA‐7867 recovered from the gastrointestinal tract at 24 h ( GI 24 h : 5.16% versus 9.21% of intravenous dose) due to impaired liver function in the rat model of dehydration. The slower Cl r could be due mainly to a significantly smaller 24 h urinary excretion of unchanged drug ( Ae 0–24 h : 4.41% versus 7.75% of intravenous dose) due to urine flow rate‐dependent Cl r of DA‐7867 in the rat model of dehydration. Hence, the Cl was significantly slower in the rat model of dehydration (0.677 versus 1.07 ml/min/kg). After intravenous administration in the rat model of dehydration, the V ss of DA‐7867 was significantly smaller than in the controls (396 versus 506 ml/kg) due mainly to significantly smaller free (unbound to plasma proteins) fractions of DA‐7867 in plasma (6.90% versus 29.2%) in the rat model of dehydration. After oral administration in the rat model of dehydration, the AUC was significantly greater than that in controls (10800 versus 7060 µg min/ml) due mainly to a significantly smaller Ae 0–24 h than in controls (3.50% and 6.17% of oral dose). Copyright © 2006 John Wiley & Sons, Ltd.