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Abnormal laboratory findings and plasma concentration monitoring of lopinavir and ritonavir in COVID‐19
Author(s) -
Batteux Benjamin,
Bodeau Sandra,
GrasChampel Valérie,
Liabeuf Sophie,
Lanoix JeanPhilippe,
Schmit JeanLuc,
Andréjak Claire,
Zerbib Yoann,
Haye Guillaume,
Masmoudi Kamel,
LemaireHurtel AnneSophie,
Bennis Youssef
Publication year - 2021
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.14489
Subject(s) - lopinavir , ritonavir , lopinavir/ritonavir , interquartile range , therapeutic drug monitoring , medicine , trough concentration , trough level , gastroenterology , pharmacokinetics , adverse effect , covid-19 , therapeutic index , pharmacology , drug , viral load , virology , virus , transplantation , disease , antiretroviral therapy , infectious disease (medical specialty) , tacrolimus
It is not known whether the adverse events (AEs) associated with the administration of lopinavir and ritonavir (LPV/r) in the treatment of COVID‐19 are concentration‐dependent. In a retrospective study of 65 patients treated with LPV/r and therapeutic drug monitoring (TDM) for severe forms of COVID‐19 (median age: 67; males: 41 [63.1%]), 33 (50.8%) displayed a grade ≥2 increase in plasma levels of hepatobiliary markers, lipase and/or triglycerides. A causal relationship between LPV/r and the AE was suspected in 9 of the 65 patients (13.8%). At 400 mg b.i.d., the plasma trough concentrations of LPV/r were high and showed marked interindividual variability (median [interquartile range]: 16,600 [11,430–20,842] ng/ml for lopinavir and 501 [247–891] ng/ml for ritonavir). The trough lopinavir concentration was negatively correlated with body mass index, while the trough ritonavir concentration was positively correlated with age and negatively correlated with prothrombin activity. However, the occurrence of abnormal laboratory values was not associated with higher trough plasma concentrations of LPV/r. Further studies will be needed to determine the value of TDM in LPV/r‐treated patients with COVID‐19.