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[Studies on the pharmacokinetics of lidamycin in mice and dogs using bioassay]
Shu-zhen Chen1, Zhong-ming Tang, Yong-su Zhen
1Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Aim:
A bioassay method was established for the determination of active concentrations of lidamycin and studied its pharmacokinetics in mice and dogs.
Methods:
Cytotoxicity of lidamycin in vitro was used to determine drug serum concentrations in vivo.
Results:
Validity of methodology met the requirements of pharmacokinetic study. The concentration-time profile in mice after iv lidamycin of 100, 50 and 10 microg x kg(-1) was best fitted with 2-compartmental model with T1/2alpha and T1/2beta of 0.77-1.8 min and 5.6-7.2 min, respectively. The AUC were 2851.3, 887.8 and 166.4 microg x min x L(-1), respectively and increased with dose nonlinearly. There were similar trends between AUC and the potency of tumor growth inhibition. After iv lidamycin of 12 microg x kg(-1) in dogs, the concentrations of lidamycin decreased rapidly and the AUC was 16 microg x min x L(-1), which were lower and quicker than those in mice. The levels in serum after second administration at day 15, were lower than those of the first.
Conclusion:
Active concentrations and pharmacokinetics of lidamycin were obtained by bioassay method successfully. There are species differences and single and multi-dosing differences in the pharmacokinetics of lidamycin.
