Mechanism of renal excretion of FK027 in dogs and rabbits.

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Abstract
The mechanism of renal excretion of FK027, a new oral cephalosporin, was investigated in dogs and rabbits. In dogs, FK027 was mainly cleared by glomerular filtration, and approximately 50% of the filtered drug was reabsorbed through the proximal tubules. This tubular reasorption and a high binding ratio to serum protein lead to exceptionally long serum half-life of the drug. The facts that the clearance ratio of FK027 declined slightly from 58.0 to 49.2% by the addition of probenecid, and that the effect of probenecid was less marked in the stop-flow study, along with no significant change in serum half-life, may account for the scarcely detectable secretion from the renal tubules. In rabbits, the addition of probenecid caused a decreased of the clearance ratio of FK027, disappearance of FK027 peak in the stop-flow study, and extended the serum half-life. These facts are evidence that FK027 is excreted by both tubular secretion and glomerular filtration in rabbits.

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