How to Handle Delayed or Missed Doses: A Population Pharmacokinetic Perspective

  • Jia-qin Gu
  • Yun-peng Guo
  • Zheng JiaoEmail author
  • Jun-jie Ding
  • Guo-Fu LiEmail author
Review Article


Delayed or missed doses are unavoidable in clinical practice and remain as a challenge that threatens a patient’s health and quality-of-life, especially in the pharmacotherapy of chronic disease treatment. Unfortunately, information or guidance concerning the management of delayed or missed doses is scarce, precluding clinicians or clinical pharmacologists from instructing patients in a precision dosing manner. It is therefore urgent to develop remedial strategies to inform patients of alternative dosing regimens in compensation for the loss of efficacy due to delayed or missed doses and minimize unintended clinical consequences. Studies aiming to establish remedial regimens have been conducted since the 1980s for oral contraceptives and antihypertensive agents, using the controlled substitution of placebos for active medications. However, it appeared to be unethical in many areas of pharmacotherapy due to deliberately discontinuing or restarting the medication. Alternatively, pharmacometric modeling and simulation offers an opportunity to investigate the effect of various non-adherence scenarios on pharmacokinetic profiles and establish the optimum remedial dosing regimen in a time-effective and systematical way. This review provides a general overview of procedures and strategies on how to develop remedial dosing regimens based on pharmacometric approaches through the scrutiny of case examples in the literature.


Compliance with Ethical Standards


This work was supported by grants from the National Natural Science Foundation of China (No.81573505), and ‘Weak Discipline Construction Project’ (No. 2016ZB0301-01) of Shanghai Municipal Commission of Health and Family Planning. The funding organizations played no role in the preparation, review, or approval of the article.

Conflict of interest

The authors have no conflicts of interest that are directly relevant to the contents of this review article.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PharmacyShanghai Chest Hospital, Shanghai Jiao Tong UniversityShanghaiPeople’s Republic of China
  2. 2.Huashan Hospital, Fudan UniversityShanghaiPeople’s Republic of China
  3. 3.China Pharmaceutical UniversityNanjingPeople’s Republic of China
  4. 4.World Wide Antimalarial Resistance Network, Centre for Tropical Medicine and Global Health, Nuffield Department of MedicineOxford UniversityOxfordUK
  5. 5.Institution of Drug Clinical TrialSubei People’s HospitalYangzhouPeople’s Republic of China

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