The Pharmacokinetics of PNU-177553 in Normal and Uninephrectomized Rats
El-Shamaa, Nancy N.
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PNU-177553 is an oxazolidinone drug candidate for a community use antibiotic (Stryd, et aI, Phannacia Corporation, 1999). Renal excretion is one of the major pathways of elimination of PNU-177553, an antibacterial compound, in animals and in humans. Renal function impairment affects the pharmacokinetics of PNU-177553, which were studied in selective models of renal impairment induced by uninephrectomized rats. This study evaluated the pharmacokinetics of PNU-177553 in rats with induced renal function impairment. Timed plasma samples were collected after administration of a single dose (either of high concentration or of low concentration) of PNU-177553 to groups of rats with induced renal function impairment and in control animals. The concentrations of PNU-177553 in the plasma and urine samples were assayed. The pharmacokinetics were compared between control rats with normal renal function, uninephrectomized rats, and between rats that received high doses of the compound and rats that received low doses of the compound. The objectives of the studies were to evaluate the changes in the pharmacokinetics of PNU-177553 in rats with induced renal function impairment and whether the phannacokinetics differ between the two doses of PNU-177553 administered. The study may provide useful data for understanding of renal elimination of PNU-177553 and other drugs in humans.