Elsevier

Antiviral Research

Volume 181, September 2020, 104866
Antiviral Research

Invited Review
Concerns about pharmacokinetic (PK) and pharmacokinetic-pharmacodynamic (PK-PD) studies in the new therapeutic area of COVID-19 infection

https://doi.org/10.1016/j.antiviral.2020.104866Get rights and content

Highlights

  • Available pharmacokinetic and pharmacodynamic studies on COVID-19 repurposed drugs suffer from severe limitations.

  • This may lead to unreliable conclusions, especially in term of dosing optimization.

  • We propose to identify the major requirements that need to be addressed in designing PK and PD studies in this era of COVID.

Abstract

In the context of the COVID-19 pandemic, several drugs have been repurposed as potential candidates for the treatment of COVID-19 infection. While preliminary choices were essentially based on in vitro potency, clinical translation into effective therapies may be challenging due to unfavorable in vivo pharmacokinetic properties at the doses chosen for this new indication of COVID-19 infection. However, available pharmacokinetic and pharmacokinetic-pharmacodynamic studies suffer from severe limitations leading to unreliable conclusions, especially in term of dosing optimization.

In this paper we propose to highlight these limitations and to identify some of the major requirements that need to be addressed in designing PK and PK-PD studies in this era of COVID. A special attention should be paid to pre-analytical and analytical requirements and to the proper collection of covariates affecting dose-exposure relationships (co-medications, use of specific organ support techniques and other clinical and para-clinical data). We also promote the development of population PK and PK-PD models specifically dedicated to COVID-19 patients since those previously developed for other diseases (SEL, malaria, HIV) and clinical situations (steady-state, non-ICU patients) are not representative of severe patients.

Therefore, implementation of well-designed PK and PD studies targeted to COVID-19 patients is urgently needed. For that purpose we call for multi-institutional collaborative work and involvement of clinical pharmacologists in multidisciplinary research consortia.

Keywords

COVID-19
Pharmacokinetics
Pharmacodynamics
PK-PD

Cited by (0)

1

Both authors contributed equally to this manuscript.

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