In clinical practice, the curative effect of drugs will decrease due to the increase of drug resistance, especially in stable long-term drug delivery systems. Intermittent drug dosing is an effective method to reduce drug resistance and achieve a better effect comparing with consistent one. The relationship between drug concentration and effect can be described by pharmacokinetics-pharmacodynamics (PK-PD) model, and a more suitable drug delivery strategy can be obtained through analysis. In this paper, a periodic dosing strategy is proposed based on a simple PK-PD model of tolerance. Through the analysis of this model, a pulse drug delivery strategy is established, which is corresponding to the rhythm of human body and easy for drug design. By discretizing the differential equations into algebraic equations based on the collocation method, the drug delivery strategy is optimized. Then, the optimized drug delivery system is simulated by the fourth-order Runge-Kutta method. Based on this method, a reference for designing a drug delivery system can be provided to reduce unnecessary dosage and improve drug efficacy.