JIANG Jiahao, JIN Zhong, LI Jun, WU Xiaotian
Mathematical analysis of pharmacokinetic models plays an important role in drug researches. In this paper, considering a one-compartment pharmacokinetic model with parallel first-order and Hill (n = 2) elimination under different dosage designs with periodic intravenous bolus administrations, we have mathematically studied the steady-state pharmacokinetics. As a result, we have proved that the pharmacokinetic model, represented by an impulsive differential equation, admits a unique steady-state periodic solution. Then we have derived the analytical formulas for two important pharmacokinetic indexes: steady-state drug exposure and steady-state average plasma concentration. Moreover, different to the existing the pharmacokinetic model with parallel first-order and Michaelis elimination pathways, we have been able to discover, both numerically and theoretically, the diversity in the steady-state average plasma concentration for different dose regimens. That is, by increasing the dosing frequency, three circumstances can occur for the steady-state average drug concentration: (i) monotonically decreases and converges to a limit value; (ii) monotonically increases and converges to a limit value; and (iii) decreases first and then increases and eventually converges to a limit value. Finally, we have applied the results to a real drug model of recombinant granulocyte colony-stimulating factor (Filgrastim), for which we have provided the analytical formulas of the steady-state average plasma concentrations using different dose regimens and calculated the steady-state average plasma concentration and minimum plasma concentration.