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Pharmacokinetics under the COVID‐19 storm
Author(s) -
Pilla Reddy Venkatesh,
ElKhateeb Eman,
Jo Heeseung,
Giovino Natalie,
Lythgoe Emily,
Sharma Shringi,
Tang Weifeng,
Jamei Masoud,
RastomiHodjegan Amin
Publication year - 2023
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.14668
Subject(s) - covid-19 , storm , pharmacokinetics , pandemic , cytokine storm , virology , medicine , meteorology , geography , pharmacology , outbreak , infectious disease (medical specialty) , disease
Aims The storm‐like nature of the health crises caused by COVID‐19 has led to unconventional clinical trial practices such as the relaxation of exclusion criteria. The question remains: how can we conduct diverse trials without exposing subgroups of populations to potentially harmful drug exposure levels? The aim of this study was to build a knowledge base of the effect of intrinsic/extrinsic factors on the disposition of several repurposed COVID‐19 drugs. Methods Physiologically based pharmacokinetic (PBPK) models were used to study the change in the pharmacokinetics (PK) of drugs repurposed for COVID‐19 in geriatric patients, different race groups, organ impairment and drug‐drug interactions (DDIs) risks. These models were also used to predict epithelial lining fluid (ELF) exposure, which is relevant for COVID‐19 patients under elevated cytokine levels. Results The simulated PK profiles suggest no dose adjustments are required based on age and race for COVID‐19 drugs, but dose adjustments may be warranted for COVID‐19 patients also exhibiting hepatic/renal impairment. PBPK model simulations suggest ELF exposure to attain a target concentration was adequate for most drugs, except for hydroxychloroquine, azithromycin, atazanavir and lopinavir/ritonavir. Conclusion We demonstrate that systematically collated data on absorption, distribution, metabolism and excretion, human PK parameters, DDIs and organ impairment can be used to verify simulated plasma and lung tissue exposure for drugs repurposed for COVID‐19, justifying broader patient recruitment criteria. In addition, the PBPK model developed was used to study the effect of age and ethnicity on the PK of repurposed drugs, and to assess the correlation between lung exposure and relevant potency values from in vitro studies for SARS‐CoV‐2.