Pharmacokinetic-pharmacodynamic binding model of febrile rats in vivo for study on epigoitrin from total alkaloids of Radix Isatidis / 中草药

ABSTRACT

Objective To investigate the relationship between pharmacokinetics(PK) and pharmacodynamics PD of epigoitrin,a main component in total alkaloids of Radix Isatidis,in yeast-induced febrile rats with the combined PK-PD model.Methods The plasma concentration of epigoitrin after ig administration with total alkaloids of Radix Isatidis was determined by HPLC method and the body temperature was recorded by electronic thermometer.The individual PK parameters were fitted using one compartmental model.The PD parameters were fitted by three kinds of PK-PD binding models,such as indirect inhibition-Kin model,indirect stimulation KoutPD model,and Sigmoid-Emax model.Results The main PK parameters t1/2,Cmax,AUC were(4.94?0.84) h,(4.01?0.21) ?g/mL,(28.37?2.42) ?g?h/mL and(5.71?0.91) h,(4.15?0.25) ?g/mL,(30.35?2.58) ?g?h/mL in both normal and febrile rats,respectively.The relationship between pharmacological effects and effect compartment concentration was better fitted with the indirect inhibition-Kin PD model.The corresponding PD parameters were Kin=(0.70?0.10) h-1,Kout=(0.54?0.12) h-1,R0=1.33?0.16,IC50=(0.94?0.66) mg/L.ConclusionThe PK parameters of epigoitrin in total alkaloids of Radix Isatidis show that there is no significant difference in PD behavior in vivo in both normal and febrile rats.Relationship between in vivo PK and PD of epigoitrin in febrile rats is established using indirect inhibition Kin model.