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Matsubayashi, K. et al.

Nonlinear pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in rats caused by non-Michaelis-Menten type, dose-dependent renal clearance.

The pharmacokinetics and its dose dependency of a new cephalosporin, DQ-2556, were studied in the rat and rabbit. The pharmacokinetics of the compound in the rat was linear up to a dose of 300 mg/kg; however, at a dose of 1200 mg/kg, renal clearance decreased dramatically and the normalized area under the blood concentration-time curve increased remarkably. On the other hand, there were no dose-dependent changes in tissue/serum concentration ratios, serum protein binding, red cell binding, and the distribution of DQ-2556. In the rabbit, the pharmacokinetics of DQ-2556 was linear even up to a dose of 1200 mg/kg and no unusual pharmacokinetic behavior was observed. The renal clearance experiments demonstrated that DQ-2556 is excreted by glomerular filtration. It was also shown that the glomerular filtration rate (GFR) remained constant up to a dose of 1000 mg/kg of DQ-2556 in the rat, whereas the GFR decreased by 95.1% at a dose of 1200 mg/kg. The coincidence of dose relationship and species difference in the disorder of GFR and renal toxicity suggests that the change of pharmacokinetics of DQ-2556 was caused by its renal toxic effects at very high dose.[1]

References

Nonlinear pharmacokinetics of DQ-2556, a new 3-quaternary ammonium cephalosporin antibiotic, in rats caused by non-Michaelis-Menten type, dose-dependent renal clearance. Matsubayashi, K., Shintani, S., Yoshida, K., Yamada, M., Tachizawa, H. Journal of pharmaceutical sciences. (1994) [Pubmed]

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