PMID- 32692462
OWN - NLM
STAT- MEDLINE
DCOM- 20210311
LR  - 20221207
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 87
IP  - 3
DP  - 2021 Mar
TI  - Abnormal laboratory findings and plasma concentration monitoring of lopinavir and 
      ritonavir in COVID-19.
PG  - 1547-1553
LID - 10.1111/bcp.14489 [doi]
AB  - 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.
CI  - (c) 2020 The British Pharmacological Society.
FAU - Batteux, Benjamin
AU  - Batteux B
AUID- ORCID: 0000-0001-9466-7110
AD  - Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
AD  - MP3CV laboratory, EA 7517, Jules Verne University of Picardie, Amiens, France.
FAU - Bodeau, Sandra
AU  - Bodeau S
AD  - Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
AD  - MP3CV laboratory, EA 7517, Jules Verne University of Picardie, Amiens, France.
FAU - Gras-Champel, Valerie
AU  - Gras-Champel V
AD  - Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
AD  - MP3CV laboratory, EA 7517, Jules Verne University of Picardie, Amiens, France.
FAU - Liabeuf, Sophie
AU  - Liabeuf S
AUID- ORCID: 0000-0001-5384-9006
AD  - Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
AD  - MP3CV laboratory, EA 7517, Jules Verne University of Picardie, Amiens, France.
AD  - Department of Clinical Research, Amiens University Hospital, Amiens, France.
FAU - Lanoix, Jean-Philippe
AU  - Lanoix JP
AD  - Department of Infectious Diseases, Amiens University Hospital, Amiens, France.
AD  - AGIR, EA 4294, Jules Verne University of Picardie, Amiens, France.
FAU - Schmit, Jean-Luc
AU  - Schmit JL
AD  - Department of Infectious Diseases, Amiens University Hospital, Amiens, France.
AD  - AGIR, EA 4294, Jules Verne University of Picardie, Amiens, France.
FAU - Andrejak, Claire
AU  - Andrejak C
AD  - AGIR, EA 4294, Jules Verne University of Picardie, Amiens, France.
AD  - Department of Pulmonology, Amiens University Hospital, Amiens, France.
FAU - Zerbib, Yoann
AU  - Zerbib Y
AUID- ORCID: 0000-0002-9937-6096
AD  - Department of Intensive Care and BoReal study group, Amiens University Hospital, 
      Amiens, France.
FAU - Haye, Guillaume
AU  - Haye G
AD  - Department of Anaesthesiology and Critical Care Medicine, Amiens University 
      Hospital, Amiens, France.
FAU - Masmoudi, Kamel
AU  - Masmoudi K
AD  - Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
FAU - Lemaire-Hurtel, Anne-Sophie
AU  - Lemaire-Hurtel AS
AD  - Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
FAU - Bennis, Youssef
AU  - Bennis Y
AUID- ORCID: 0000-0002-0186-4797
AD  - Department of Clinical Pharmacology, Amiens University Hospital, Amiens, France.
AD  - MP3CV laboratory, EA 7517, Jules Verne University of Picardie, Amiens, France.
LA  - eng
GR  - Amiens University Hospital/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200803
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Anti-Retroviral Agents)
RN  - 2494G1JF75 (Lopinavir)
RN  - 9001-26-7 (Prothrombin)
RN  - O3J8G9O825 (Ritonavir)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Aging/metabolism
MH  - Anti-Retroviral Agents/*adverse effects/*blood/therapeutic use
MH  - Body Mass Index
MH  - COVID-19/*blood
MH  - Female
MH  - Humans
MH  - Lopinavir/*adverse effects/*blood/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Prothrombin/analysis
MH  - Retrospective Studies
MH  - Ritonavir/*adverse effects/*blood/therapeutic use
MH  - COVID-19 Drug Treatment
OTO - NOTNLM
OT  - adverse drug reactions
OT  - antiretroviral drug
OT  - hepatotoxicity
OT  - pharmacovigilance
OT  - therapeutic drug monitoring
EDAT- 2020/07/22 06:00
MHDA- 2021/03/12 06:00
CRDT- 2020/07/22 06:00
PHST- 2020/05/02 00:00 [received]
PHST- 2020/06/22 00:00 [revised]
PHST- 2020/07/13 00:00 [accepted]
PHST- 2020/07/22 06:00 [pubmed]
PHST- 2021/03/12 06:00 [medline]
PHST- 2020/07/22 06:00 [entrez]
AID - 10.1111/bcp.14489 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2021 Mar;87(3):1547-1553. doi: 10.1111/bcp.14489. Epub 2020 
      Aug 3.