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Article: Transient Lactic Acidosis and Elevation of Transaminases after the Introduction of Remdesivir in a Patient with Acute Kidney Injury.

André, Elise / Lemaitre, Florian / Verdier, Marie-Clémence / Haufroid, Vincent / Pereira, João Pinto / Hantson, Philippe

Case reports in critical care

2024 Volume 2024, Page(s) 6631866

Abstract: A 56-year-old woman was transferred to the intensive care unit (ICU) two days after an allogeneic stem cell transplantation (ASCT) when she presented acute respiratory distress due to the relapse of a SARS-CoV-2 infection. Following that, she received ... ...

Abstract	A 56-year-old woman was transferred to the intensive care unit (ICU) two days after an allogeneic stem cell transplantation (ASCT) when she presented acute respiratory distress due to the relapse of a SARS-CoV-2 infection. Following that, she received two intravenous doses of 100 mg remdesivir. Subsequently, the patient developed multiple instances of diarrhea, progressing to oliguria and acute kidney injury, necessitating continuous venovenous hemofiltration (CVVH). Despite the absence of signs of hypoxemia or cardiocirculatory failure requiring vasopressor intervention, a progressive lactic acidosis emerged. Two days after the onset of lactic acidosis, a significant rise in aminotransferases and lactate dehydrogenase occurred, in the absence of encephalopathy and coagulation disorders. Remdesivir therapy had been interrupted upon the initial signs of lactic acidosis. Despite an improvement in liver function tests and lactic acidosis, the patient's condition deteriorated, ultimately leading to her demise on day 29 due to newly arising hematological complications.
Language	English
Publishing date	2024-02-22
Publishing country	United States
Document type	Case Reports
ZDB-ID	2927720-6
ISSN	2090-6439 ; 2090-6420
ISSN (online)	2090-6439
ISSN	2090-6420
DOI	10.1155/2024/6631866
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Atorvastatin-associated myotoxicity: A toxicokinetic review of pharmacogenetic associations to evaluate the feasibility of precision pharmacotherapy.

Hoste, Emilia / Haufroid, Vincent / Deldicque, Louise / Balligand, Jean-Luc / Elens, Laure

Clinical biochemistry

2024 Volume 124, Page(s) 110707

Abstract: Atorvastatin (ATV) and other statins are highly effective in reducing cholesterol levels. However, in some patients, the development of drug-associated muscle side effects remains an issue as it compromises the adherence to treatment. Since the toxicity ... ...

Abstract	Atorvastatin (ATV) and other statins are highly effective in reducing cholesterol levels. However, in some patients, the development of drug-associated muscle side effects remains an issue as it compromises the adherence to treatment. Since the toxicity is dose-dependent, exploring factors modulating pharmacokinetics (PK) appears fundamental. The purpose of this review aims at reporting the current state of knowledge about the singular genetic susceptibilities influencing the risk of developing ATV muscle adverse events through PK modulations. Multiple single nucleotide polymorphisms (SNP) in efflux (ABCB1, ABCC1, ABCC2, ABCC4 and ABCG2) and influx (SLCO1B1, SLCO1B3 and SLCO2B1) transporters have been explored for their association with ATV PK modulation or with statin-related myotoxicities (SRM) development. The most convincing pharmacogenetic association with ATV remains the influence of the rs4149056 (c.521 T > C) in SLCO1B1 on ATV PK and pharmacodynamics. This SNP has been robustly associated with increased ATV systemic exposure and consequently, an increased risk of SRM. Additionally, the SNP rs2231142 (c.421C > A) in ABCG2 has also been associated with increased drug exposure and higher risk of SRM occurrence. SLCO1B1 and ABCG2 pharmacogenetic associations highlight that modulation of ATV systemic exposure is important to explain the risk of developing SRM. However, some novel observations credit the hypothesis that additional genes (e.g. SLCO2B1 or ABCC1) might be important for explaining local PK modulations within the muscle tissue, indicating that studying the local PK directly at the skeletal muscle level might pave the way for additional understanding.
MeSH term(s)	Humans ; Atorvastatin/adverse effects ; Atorvastatin/pharmacokinetics ; Pharmacogenetics ; Feasibility Studies ; Toxicokinetics ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Polymorphism, Single Nucleotide ; Liver-Specific Organic Anion Transporter 1/genetics
Chemical Substances	Atorvastatin (A0JWA85V8F) ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; SLCO1B1 protein, human ; Liver-Specific Organic Anion Transporter 1
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	390372-2
ISSN	1873-2933 ; 0009-9120
ISSN (online)	1873-2933
ISSN	0009-9120
DOI	10.1016/j.clinbiochem.2024.110707
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Zs.A 624: Show issues

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Article ; Online: Unconjugated Hyperbilirubinemia in Acetaminophen-Related Acute Liver Failure.

Philippart, Marie / Mesland, Jean-Baptiste / Haufroid, Vincent / Collienne, Christine / Hantson, Philippe

The American journal of case reports

2024 Volume 25, Page(s) e942703

Abstract: BACKGROUND In the absence of liver transplantation, the natural history of acetaminophen-induced liver failure is characterized by a progressive increase of liver function tests, including bilirubin mainly as its conjugated form. The presence of high ... ...

Abstract	BACKGROUND In the absence of liver transplantation, the natural history of acetaminophen-induced liver failure is characterized by a progressive increase of liver function tests, including bilirubin mainly as its conjugated form. The presence of high levels of unconjugated bilirubin is more unusual; its etiology is unclear and its prognostic factor has been poorly investigated. CASE REPORT A 52-year-old man with a history of chronic analgesics, alcohol, and illicit drug abuse developed acute liver failure in relationship with the ingestion of largely supra-therapeutic doses of acetaminophen over the days preceding admission. The patient received the classical N-acetylcysteine treatment regimen for acetaminophen overdose. Clinical course was characterized by a progressive worsening of the neurological condition, evolving to grade IV encephalopathy. Coagulation disorders persisted, with factor V level <10%. He fulfilled the criteria for liver transplantation, but this option was rejected after a careful psychiatric evaluation. Laboratory investigations revealed a progressive increase in serum unconjugated bilirubin until his death. As evidence for hemolysis was lacking, acquired deficit in bilirubin glucuronidation appeared likely and diagnosis of Gilbert's syndrome was excluded. CONCLUSIONS After the exclusion of other causes of high unconjugated bilirubin levels, the progressive increase in unconjugated bilirubin can reflect a persistent defect in bilirubin conjugation in relationship with liver centrilobular injury, but the relationship with acetaminophen-glucuronidation is not known and there are insufficient data to affirm that the ratio unconjugated/conjugated bilirubin could be used as a prognostic factor.
MeSH term(s)	Male ; Humans ; Middle Aged ; Acetaminophen/adverse effects ; Hyperbilirubinemia/chemically induced ; Hyperbilirubinemia/diagnosis ; Gilbert Disease/diagnosis ; Liver ; Bilirubin ; Liver Failure, Acute/chemically induced ; Liver Failure, Acute/diagnosis
Chemical Substances	Acetaminophen (362O9ITL9D) ; Bilirubin (RFM9X3LJ49)
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2517183-5
ISSN	1941-5923 ; 1941-5923
ISSN (online)	1941-5923
ISSN	1941-5923
DOI	10.12659/AJCR.942703
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Article ; Online: Pharmacogenetics Biomarkers Predictive of Drug Pharmacodynamics as an Additional Tool to Therapeutic Drug Monitoring.

Haufroid, Vincent / Picard, Nicolas

Therapeutic drug monitoring

2019 Volume 41, Issue 2, Page(s) 121–130

Abstract: Conventional therapeutic drug monitoring refers to the individualization of drug dosage by maintaining plasma or blood drug concentrations within a targeted therapeutic range. Accordingly, an individualized dose is proposed to the clinician according to ... ...

Abstract	Conventional therapeutic drug monitoring refers to the individualization of drug dosage by maintaining plasma or blood drug concentrations within a targeted therapeutic range. Accordingly, an individualized dose is proposed to the clinician according to the drug plasma or blood concentration using an a posteriori approach. Pharmacogenetics (PGx) has recently emerged as an additional tool to refine dose selection or, more interestingly to select, a priori, the first dose to administer. To date, the vast majority of genes explored in the context of PGx are those coding for metabolizing enzymes or membrane drug transporters, which mainly influence drug pharmacokinetics parameters. Indeed, among the 94 PGx-based drug dosing guidelines currently published by the Clinical Pharmacogenetics Implementation Consortium and the Dutch Pharmacogenetics Working Group on PharmGKB web site, 81 (86%) are associated with the genotype determination of either a metabolizing enzyme or a membrane drug transporter, whereas only 13 (14%) are associated with the genotype determination of a pharmacodynamics (PD)-associated gene. In this article, we describe selected PGx biomarkers that predict or could predict PD (both in terms of efficacy and toxicity). First, the most relevant clinical applications already subject to validated international guidelines (Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group), and ready to be implemented in routine clinical settings, are discussed to illustrate the clinical potential of PD-associated PGx biomarkers (G6PD, HLA-B57:01, HLA-B15:02, and VKORC1). Then, to illustrate not only the research potential of such biomarkers but also the complexity of PGx-PD relationships, the case of immunosuppressive drugs (for which conventional therapeutic drug monitoring is widely accepted) is extensively described with the potential to include some of these PGx biomarkers in future PGx dosing guidelines.
MeSH term(s)	Drug Monitoring/methods ; Genetic Markers ; Humans ; Immunosuppressive Agents/therapeutic use ; Pharmacogenetics
Chemical Substances	Genetic Markers ; Immunosuppressive Agents
Language	English
Publishing date	2019-02-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	424443-6
ISSN	1536-3694 ; 0163-4356
ISSN (online)	1536-3694
ISSN	0163-4356
DOI	10.1097/FTD.0000000000000591
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Zs.A 1503: Show issues

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Article ; Online: Lactic acidosis after allogeneic haematopoietic stem cell transplantation potentially related to letermovir.

Manczak, Bérénice / Verdier, Marie-Clémence / Dewulf, Joseph P / Lemaitre, Florian / Haufroid, Vincent / Hantson, Philippe

British journal of clinical pharmacology

2023 Volume 89, Issue 5, Page(s) 1686–1689

Abstract: A 53-year-old woman with a history of acute myeloid leukaemia received a second allogeneic haematopoietic stem cell transplant and was prescribed, among other medications, acyclovir and letermovir (480-mg daily oral dose) for prophylaxis of, respectively, ...

Abstract	A 53-year-old woman with a history of acute myeloid leukaemia received a second allogeneic haematopoietic stem cell transplant and was prescribed, among other medications, acyclovir and letermovir (480-mg daily oral dose) for prophylaxis of, respectively, herpes simplex and cytomegalovirus infection. The patient was admitted in the intensive care unit for dyspnoea and oliguria. Laboratory investigations revealed acute kidney injury but also a severe and progressive lactic acidosis. Liver function tests were within normal range. The combination of lactic acidosis, hypoglycaemia and acylcarnitine profile in plasma raised the suspicion of mitochondrial toxicity. Letermovir therapy was interrupted, and determination of plasma letermovir pharmacokinetics revealed a prolonged terminal half-life (38.7 h) that was not significantly influenced by continuous venovenous haemofiltration. Exploration for genetic polymorphisms revealed that the patient was SLCO1B15/15 (c.521T>C homozygous carrier and c.388A>G heterozygous carrier) with a predicted nonfunctional organic anion transporting polypeptide 1B1 protein. The relationship between letermovir accumulation and development of lactic acidosis requires further observations.
MeSH term(s)	Female ; Humans ; Middle Aged ; Acidosis, Lactic/therapy ; Acidosis, Lactic/drug therapy ; Antiviral Agents/therapeutic use ; Cytomegalovirus Infections/drug therapy ; Acetates/pharmacokinetics ; Hematopoietic Stem Cell Transplantation/adverse effects ; Liver-Specific Organic Anion Transporter 1
Chemical Substances	letermovir (1H09Y5WO1F) ; Antiviral Agents ; Acetates ; SLCO1B1 protein, human ; Liver-Specific Organic Anion Transporter 1
Language	English
Publishing date	2023-02-19
Publishing country	England
Document type	Case Reports
ZDB-ID	188974-6
ISSN	1365-2125 ; 0306-5251 ; 0264-3774
ISSN (online)	1365-2125
ISSN	0306-5251 ; 0264-3774
DOI	10.1111/bcp.15686
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Zs.A 1118: Show issues

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Article ; Online: Heavy metal chelation tests: the misleading and hazardous promise.

Hoet, Perrine / Haufroid, Vincent / Lison, Dominique

Archives of toxicology

2020 Volume 94, Issue 8, Page(s) 2893–2896

Language	English
Publishing date	2020-07-16
Publishing country	Germany
Document type	Editorial
ZDB-ID	124992-7
ISSN	1432-0738 ; 0340-5761
ISSN (online)	1432-0738
ISSN	0340-5761
DOI	10.1007/s00204-020-02847-7
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Uf I Zs.90: Show issues

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Article ; Online: Intravenous Lipid Emulsion in a Case of Trazodone Overdose.

Nendumba, Gauthier / Boland, Lidvine / Haufroid, Vincent / Laterre, Pierre-François / Hantson, Philippe

The primary care companion for CNS disorders

2022 Volume 24, Issue 2

MeSH term(s)	Antidepressive Agents/therapeutic use ; Drug Overdose/therapy ; Fat Emulsions, Intravenous/therapeutic use ; Humans ; Trazodone
Chemical Substances	Antidepressive Agents ; Fat Emulsions, Intravenous ; Trazodone (YBK48BXK30)
Language	English
Publishing date	2022-03-08
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	2675414-9
ISSN	2155-7780 ; 2155-7780
ISSN (online)	2155-7780
ISSN	2155-7780
DOI	10.4088/PCC.21cr02994
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Article ; Online: Elevation of alkaline phosphatase and long-term drug therapy for cystic fibrosis.

Delmez, Quentin / Haufroid, Vincent / Gohy, Sophie / Laterre, Pierre-François / Hantson, Philippe

European journal of clinical pharmacology

2022 Volume 78, Issue 4, Page(s) 699–701

MeSH term(s)	Alkaline Phosphatase/therapeutic use ; Benzodioxoles ; Cystic Fibrosis/drug therapy ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/therapeutic use ; Humans ; Mutation
Chemical Substances	Benzodioxoles ; Cystic Fibrosis Transmembrane Conductance Regulator (126880-72-6) ; Alkaline Phosphatase (EC 3.1.3.1)
Language	English
Publishing date	2022-01-15
Publishing country	Germany
Document type	Letter
ZDB-ID	121960-1
ISSN	1432-1041 ; 0031-6970
ISSN (online)	1432-1041
ISSN	0031-6970
DOI	10.1007/s00228-021-03272-0
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Zs.A 672: Show issues

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Article ; Online: A Case Report of Safe Coadministration of Amiodarone with Short-Term Treatment Nirmatrelvir-Ritonavir.

Sluijters, Alice / Lemaitre, Florian / Belkhir, Leïla / Boland, Lidvine / Haufroid, Vincent / De Greef, Julien

Clinical pharmacology and therapeutics

2022 Volume 113, Issue 4, Page(s) 768–769

MeSH term(s)	Humans ; Amiodarone/adverse effects ; Ritonavir/adverse effects
Chemical Substances	nirmatrelvir (7R9A5P7H32) ; Amiodarone (N3RQ532IUT) ; Ritonavir (O3J8G9O825)
Language	English
Publishing date	2022-12-21
Publishing country	United States
Document type	Case Reports ; Letter ; Comment
ZDB-ID	123793-7
ISSN	1532-6535 ; 0009-9236
ISSN (online)	1532-6535
ISSN	0009-9236
DOI	10.1002/cpt.2805
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Article ; Online: Genetic polymorphisms of ATP-binding cassette transporters ABCB1 and ABCC2 and their impact on drug disposition.

Haufroid, Vincent

Current drug targets

2010 Volume 12, Issue 5, Page(s) 631–646

Abstract: The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes, and act as efflux proteins. ABC transporters are characterised by the presence of ... ...

Abstract	The ATP-binding cassette (ABC) transporter superfamily comprises membrane proteins that translocate a variety of substrates across extra- and intra-cellular membranes, and act as efflux proteins. ABC transporters are characterised by the presence of genetic polymorphisms mainly represented by single nucleotide polymorphisms (SNPs), some of which having an impact on their activity. Besides physiological substances, drugs are also substrates of some ABC transporters, mainly ABCB1, ABCC1, ABCC2, ABCC3 and ABCG2. Identifying the impact of these polymorphisms on the pharmacokinetics (PK) of these drugs may have important clinical implications, certainly for those characterised by a narrow therapeutic index and significant inter- and intra-patient PK variability. This review focuses specifically on ABCB1 and ABCC2 and critically analyses important publications dealing with the influence of ABCB1 and/or ABCC2 polymorphisms on drug disposition in humans. For different reasons discussed in this paper, the effect of ABCB1 and/or ABCC2 polymorphisms on drug concentrations in blood is not always easy to interpret and to correlate with pharmacological effects. In contrast, intracellular or target tissue drug concentrations appear more directly influenced by these polymorphisms, as illustrated with intralymphocyte concentrations for immunosupressants and antiretrovirals or with cerebrospinal fluid (CSF) concentrations for antiepileptics and antidepressants. Further research on intracellular and/or target tissue drug concentrations are still needed to better characterise the PK-PG (pharmacogenetics) relationship involving ABC transporters.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; ATP-Binding Cassette Transporters/genetics ; ATP-Binding Cassette Transporters/physiology ; Drug Resistance, Multiple/genetics ; Female ; Humans ; Male ; Multidrug Resistance-Associated Proteins/genetics ; Multidrug Resistance-Associated Proteins/metabolism ; Pharmaceutical Preparations/metabolism ; Polymorphism, Genetic ; Polymorphism, Single Nucleotide
Chemical Substances	ABCB1 protein, human ; ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; ATP-Binding Cassette Transporters ; Multidrug Resistance-Associated Proteins ; Pharmaceutical Preparations ; multidrug resistance-associated protein 2 (4AF605U6JN)
Language	English
Publishing date	2010-10-10
Publishing country	United Arab Emirates
Document type	Journal Article ; Review
ZDB-ID	2064859-5
ISSN	1873-5592 ; 1389-4501
ISSN (online)	1873-5592
ISSN	1389-4501
DOI	10.2174/138945011795378487
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