Elimination kinetics of amsacrine in the rabbit: evidence of nonlinearity.
Plasma amsacrine kinetics have been studied in rabbits after different doses (2.5-10 mg/kg) infused over 35 min. Amsacrine concentrations were measured by HPLC and plasma protein binding by equilibrium dialysis. All elimination curves were best fitted by a bi-exponential expression with a mean t 1/2 alpha of 0.56 h and t 1/2 beta of 2.47 h. At doses greater than 5 mg/kg, there appeared to be an overproportional increase in the area under the curve, suggesting non-linear kinetics. Comparison of pharmacokinetic parameters indicated a significant decrease in plasma Cl after the 10-mg/kg dose compared to the 5- and 2.5-mg/kg dose. Amsacrine was highly bound by plasma (96.8%) over the concentration range 1-100 mumol/l. It is concluded that the rabbit is an acceptable model for further studies of the pharmacokinetics of amsacrine and its analogues at doses less than or equal to 5 mg/kg.
D000609:Aminoacridines / Q000378:metabolism*; D000677:Amsacrine; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism; D007700:Kinetics; D011485:Protein Binding; D011817:Rabbits
D000609:Aminoacridines; D000970:Antineoplastic Agents; D001798:Blood Proteins; D000677:Amsacrine