Given that the traditional methods of estimating pharmacokinetic parameters are constrained by the sensitivity of their initial value and incapability of evolutionary algorithm to determine search range,this paper proposes a adaptive hybrid particle swarm optimization(AHPSO)algorithm by combining the Hooke-Jeeves(HJ)and particle swarm optimization(PSO)algorithm.Using the AHPSO algorithm for the parameter optimization by the experiment of extravascular administration two-compartment model,we can see that the proposed method is not only better than traditional feathering method(FM)in terms of numerical stability,but also better than HJ and PSO in terms of error minimization.The experimental results show that AHPSO algorithm is a feasible method to optimize the pharmacokinetic parameters,which has higher precision and stronger robustness than the other techniques.