幼若犬および成熟犬におけるセファロスポリン誘導体の体内動態の比較

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  • Pharmacokinetic Study of a Cepharosporin Derivative in Infant and Adult Dogs.

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The changes in pharmacokinetics of a cephalosporin derivative (Cefluprenam; CFLP) with age were studied. CFLP was administered intravenously to infant (at 3 weeks of age) or adult beagle dogs (at 8 months of age) once a day for 4 weeks at a dose of 300 mg/kg.<BR> In adult dogs, the plasma elimination half-life (t1/2) on the first day and on the 27th day of treatment was 0.91±0.030 hr and 0.90±0.031 hr, and total body clearance of CFLP (CLtot) was 0.27±0.009 l/hr/kg and 0.28±0.007 l/hr/kg, respectively. The pharmacokinetics of CFLP in adult dogs showed no change after repeated administration. Creatinine clearance (normalized per body weight) in adult dogs was 0.21 ± 0.010 l/hr/kg. These findings indicate that CFLP is excreted mainly by glomerular filtration in the kidneys.<BR> In infant dogs, on the other hand, CFLP disappeared from the plasma on the 27th day of treatment faster than on the first day. The t1/2 of CFLP on the first day (at 3 weeks of age) and on the 27th day (at 7 weeks of age) were 0.90 ± 0.15 hr and 0.61 ± 0.02 hr, respectively, and CLtot were 0.45 ± 0.03 l/hr/kg and 0.64 ±0.01 l/hr/kg, respectively. There was no notable difference in the distribution volume VI or Vss between the first day and the 27th day of treatment. Creatinine clearance which was 0.28 ± 0.05 l/hr/kg for the CFLP 300 mg/kg group of infant dogs on the first day of administration increased to 0.49 ± 0.13 l/hr/kg on the 27th day of treatment. The increase in Mot on the 27th day of treatment was resulted from an increase in creatinine clearance, that is, glomerular filtration. Since creatinine clearance was similar in the CFLPtreated group and the untreated control group, the increase in creatinine clearance was not due to repeated administration of CFLP, but to the growth of the infant dogs.<BR> The plasma levels of CFLP in infant dogs were lower than those in adult dogs, and the distribution volume Vss was higher than those in adult dogs. Because CFLP is distributed in extracellular fluid, these results seem to be caused by the water content ratio of the body which is higher in infant dogs than in adult ones.<BR> These results suggest that the changes in pharmacokinetics of CFLP are related to physiological changes in renal function and the water content of their body with age. Glomerular filtration was low in infant dogs at 3 weeks of age, but increased in a steep curve at 7 weeks of age. It appears that glomerular filtration of the drug gradually declines after the age of 7 weeks.

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  • 薬物動態

    薬物動態 14 (4), 294-299, 1999

    日本薬物動態学会

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