Program design of indirect pharmacokinetic and pharmacodynamic model

Aim: A programme was designed to obtain the parameters of indirect pharmacokinetic-pharmacodynamic model proposed by Dayneka. Methods: Using both genetic algorithm and planning solution, the parameters of the model can be estimated through simultaneous fitting of concentration-time data and response-time data. Results: Taking one compartment model following oral administration as example, the pharmacokinetic parameters value from curve fitting of the model of warfarin were: t_max(3.40 ± 1.52)h, c_max(56.39 ± 6.85)χ/ mL, t_1/2(20.14 ± 5.66)h; the pharmacodynamic parameters value were K_in(0.100 9 ± 0.019 3)h^-1, K_out(0.093 8 ± 0.017 4)h^-1,IC₅₀(3.732 ± 1.336) mg/L. Conclusion: The application of the programme in obtaining parameters value of indirect pharmacokinetic-pharmacodynamic model and characterization of the pharmacokinetic/pharmacodynanic behaviour of a drug had practical value in use.