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Article ; Online: Comment on 'Therapeutic drug monitoring-guided treatment versus standard dosing of voriconazole for invasive aspergillosis in haematological patients: A multicentre, prospective, cluster randomised, crossover clinical trial'.

Gautier-Veyret, Elodie / Thiebaut-Bertrand, Anne / Stanke-Labesque, Françoise

International journal of antimicrobial agents

2023 Volume 62, Issue 2, Page(s) 106853

MeSH term(s)	Humans ; Voriconazole/therapeutic use ; Drug Monitoring ; Prospective Studies ; Aspergillosis/drug therapy ; Antifungal Agents/therapeutic use ; Invasive Fungal Infections/drug therapy
Chemical Substances	Voriconazole (JFU09I87TR) ; Antifungal Agents
Language	English
Publishing date	2023-05-18
Publishing country	Netherlands
Document type	Randomized Controlled Trial ; Multicenter Study ; Letter ; Comment
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2023.106853
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Article ; Online: COVID-19 lockdowns and incidence of psychoactive substance exposure according to age and sex.

Spinelli, Aurélien / Willeman, Theo / Roustit, Matthieu / Stanke-Labesque, Françoise

Clinical toxicology (Philadelphia, Pa.)

2021 Volume 60, Issue 5, Page(s) 596–601

Abstract: Background: The lockdown periods imposed in 2020 by governments had deleterious consequences on population mental health. Several studies based on declarative data have suggested that the lockdown periods were associated with changes in psychoactive ... ...

Abstract	Background: The lockdown periods imposed in 2020 by governments had deleterious consequences on population mental health. Several studies based on declarative data have suggested that the lockdown periods were associated with changes in psychoactive substance use but few relied on toxicological analyses. Aims: We studied the impact of lockdowns on the pattern of routine care toxicological screening performed on patients hospitalized at the emergency ward (EW) and intensive care units (ICU) at the Grenoble University Hospital. Method: This was a retrospective, monocentric study comparing routine care toxicology biological tests performed in children older than 12 years of age and adults hospitalized at the ICU and EW in 2018, 2019, and 2020. Alcohol, illicit drugs, and medications were screened. Generalized linear models were generated to evaluate the effect of the lockdown periods on toxicology results, considering age and sex. Results: The study included 13,910 samples from 11,786 patients. There was no significant difference in the repartition of sex or age over the three years. The frequency of positive toxicological tests increased during the lockdown periods (adjusted odds ratio (OR) 95% confidence interval (CI): 1.14, (1.01-1.28), Conclusions: This study suggests that lockdown episodes were associated with increased incidence of psychoactive substance poly-exposures, highlighting the need for preventive strategies for high-risk populations.
MeSH term(s)	Adolescent ; Adult ; COVID-19/epidemiology ; Child ; Child, Preschool ; Communicable Disease Control ; Humans ; Incidence ; Male ; Retrospective Studies ; SARS-CoV-2 ; Young Adult
Language	English
Publishing date	2021-12-14
Publishing country	England
Document type	Journal Article
ZDB-ID	204476-6
ISSN	1556-9519 ; 0009-9309 ; 0731-3810 ; 1556-3650
ISSN (online)	1556-9519
ISSN	0009-9309 ; 0731-3810 ; 1556-3650
DOI	10.1080/15563650.2021.2013494
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Article: Variability of Isavuconazole Trough Concentrations during Longitudinal Therapeutic Drug Monitoring.

Bolcato, Léa / Thiebaut-Bertrand, Anne / Stanke-Labesque, Françoise / Gautier-Veyret, Elodie

Journal of clinical medicine

2022 Volume 11, Issue 19

Abstract: Isavuconazole (ISA), a triazole antifungal agent, is licensed for the treatment of invasive aspergillosis and mucormycosis. Therapeutic drug monitoring (TDM) is a cornerstone of treatment efficacy for triazole antifungals due to their pharmacokinetic ... ...

Abstract	Isavuconazole (ISA), a triazole antifungal agent, is licensed for the treatment of invasive aspergillosis and mucormycosis. Therapeutic drug monitoring (TDM) is a cornerstone of treatment efficacy for triazole antifungals due to their pharmacokinetic variability, except for ISA, for which the utility of TDM is still uncertain. We performed a retrospective study that aimed to assess the inter- and intra-individual variability of ISA trough concentrations (Cmin) and to identify the determinants involved in such variability. ISA Cmin measured in adult patients at the Grenoble Alpes University Hospital between January 2018 and August 2020 were retrospectively analyzed. In total, 304 ISA Cmin for 33 patients were analyzed. The median ISA Cmin was 2.8 [25th−75th percentiles: 2.0−3.7] mg/L. The inter- and intra-individual variability was 41.5% and 30.7%, respectively. Multivariate analysis showed independent covariate effects of dose (β = 0.004 ± 3.56 × 10−4, p < 0.001), Aspartate aminotransférase (ASAT) (β = 0.002 ± 5.41 × 10−4, p = 0.002), and protein levels (β = 0.022 ± 0.004, p < 0.001) on ISA Cmin, whereas C reactive protein levels did not show any association. This study, conducted on a large number of ISA Cmin, shows that ISA exposure exhibits variability, explained in part by the ISA dose, and ASAT and protein levels.
Language	English
Publishing date	2022-09-28
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm11195756
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Article ; Online: A Minimal PBPK Model for Plasma and Cerebrospinal Fluid Pharmacokinetics of Trastuzumab after Intracerebroventricular Administration in Patients with HER2-Positive Brain Metastatic Localizations.

Puszkiel, Alicja / Bousquet, Guilhem / Stanke-Labesque, Françoise / Stocco, Jeanick / Decq, Philippe / Chevillard, Lucie / Goutagny, Stéphane / Declèves, Xavier

Pharmaceutical research

2023 Volume 40, Issue 11, Page(s) 2687–2697

Abstract: Background: Dosing regimens of trastuzumab administered by intracerebroventricular (icv) route to patients with HER2-positive brain localizations remain empirical. The objectives of this study were to describe pharmacokinetics (PK) of trastuzumab in ... ...

Abstract	Background: Dosing regimens of trastuzumab administered by intracerebroventricular (icv) route to patients with HER2-positive brain localizations remain empirical. The objectives of this study were to describe pharmacokinetics (PK) of trastuzumab in human plasma and cerebrospinal fluid (CSF) after simultaneous icv and intravenous (iv) administration using a minimal physiologically-based pharmacokinetic model (mPBPK) and to perform simulations of alternative dosing regimens to achieve therapeutic concentrations in CSF. Methods: Plasma and CSF PK data were collected in two patients with HER2-positive brain localizations. A mPBPK model for mAbs consisting of four compartments (tight and leaky tissues, plasma and lymph) was enriched by an additional compartment for ventricular CSF. The comparison between observed and model-predicted concentrations was evaluated using prediction error (PE). Results: The developed mPBPK model described plasma and CSF trastuzumab concentrations reasonably well with mean PE for plasma and CSF data of 41.8% [interquartile range, IQR = -9.48; 40.6] and 18.3% [-36.7; 60.6], respectively, for patient 1 and 11.4% [-10.8; 28.7] and 22.5% [-27.7; 77.9], respectively, for patient 2. Trastuzumab showed fast clearance from CSF to plasma with C Conclusion: Continuous icv infusion of trastuzumab at 1.0 mg/h could be an alternative dosing regimen to rapidly achieve intraventricular CSF therapeutic concentrations.
MeSH term(s)	Humans ; Trastuzumab ; Antibodies, Monoclonal/pharmacokinetics ; Brain ; Administration, Intravenous ; Infusions, Intravenous
Chemical Substances	Trastuzumab (P188ANX8CK) ; Antibodies, Monoclonal
Language	English
Publishing date	2023-10-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-023-03614-w
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Article: Early Exposure of Kidney Transplant Recipients with Chronic Antibody-Mediated Rejection to Tocilizumab-A Preliminary Study.

Arrivé, Capucine / Jacquet, Marvin / Gautier-Veyret, Elodie / Jouve, Thomas / Noble, Johan / Lombardo, Dorothée / Rostaing, Lionel / Stanke-Labesque, Françoise

Journal of clinical medicine

2023 Volume 12, Issue 22

Abstract: Tocilizumab prevents clinical worsening of chronic antibody-mediated rejection (CAMR) of kidney transplant recipients. Optimization of this treatment is necessary. We identified the determinants of early tocilizumab exposure (within the first three ... ...

Abstract	Tocilizumab prevents clinical worsening of chronic antibody-mediated rejection (CAMR) of kidney transplant recipients. Optimization of this treatment is necessary. We identified the determinants of early tocilizumab exposure (within the first three months) and investigated the relationship between early plasma tocilizumab exposure and graft function. Patients with CAMR who started treatment with tocilizumab were retrospectively included. Demographic, clinical, and biological determinants of the tocilizumab trough concentration (C
Language	English
Publishing date	2023-11-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm12227141
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Article ; Online: Suicide with oral midazolam: Postmortem toxicological investigations using Ostro® Plate and ultra-high performance liquid chromatography coupled to tandem mass spectrometry.

Boudin, Coralie / Eysseric-Guérin, Hélène / Paysant, François / Revet, Melissa / Stanke-Labesque, Françoise / Scolan, Virginie / Willeman, Théo

Journal of analytical toxicology

2023 Volume 47, Issue 6, Page(s) 535–540

Abstract: A middle-aged woman was found dead with multiple empty blisters of midazolam (MDZ) (DORMICUM®), equivalent to 450 mg, near her body. The autopsy revealed that the cause of death was secondary to an asphyxia syndrome. Standard toxicological procedures ... ...

Abstract	A middle-aged woman was found dead with multiple empty blisters of midazolam (MDZ) (DORMICUM®), equivalent to 450 mg, near her body. The autopsy revealed that the cause of death was secondary to an asphyxia syndrome. Standard toxicological procedures identified MDZ only in blood, urine and gastric content. A quantitative analytical method for MDZ and 1-hydroxymidazolam (1-OH-MDZ) was validated using protein precipitation, a phospholipid removal Ostro® plates and liquid chromatography coupled to tandem mass spectrometry. MDZ and 1-OH-MDZ were quantified in peripheral blood at 910 and 534 ng/mL, respectively, and superior to 2000 ng/mL in urine. Reported to the body weight, the dose, which was lethal, was estimated to be 6.7 mg/kg. The usual dose used in the intensive care unit is 0.03-0.3 mg/kg. MDZ intoxication outside of hospital is rare given the restricted availably of this drug in France. Nevertheless, MDZ under oral form remains available in several countries. Toxic MDZ blood concentrations are described after intravenous administration for anesthesia and are not suited for oral intoxication. Based on the autopsy findings, police investigation and toxicology results, the cause of death was determined to be a self-inflicted oral MDZ acute intoxication, which is the first to be documented to the best of our knowledge. This fatal intoxication provides analytical data that could support subsequent toxicological result interpretation in similar forensic cases.
MeSH term(s)	Humans ; Female ; Middle Aged ; Midazolam ; Tandem Mass Spectrometry/methods ; Chromatography, High Pressure Liquid ; Autopsy ; Suicide
Chemical Substances	Midazolam (R60L0SM5BC)
Language	English
Publishing date	2023-06-21
Publishing country	England
Document type	Journal Article
ZDB-ID	752391-9
ISSN	1945-2403 ; 0146-4760
ISSN (online)	1945-2403
ISSN	0146-4760
DOI	10.1093/jat/bkad032
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Zs.A 1333: Show issues

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Article ; Online: Trends in drivers testing positive for drugs of abuse in oral fluid from 2018 to 2021 in France.

Willeman, Théo / Bartolli, Mireille / Jourdil, Jean-François / Vial, Simon / Eysseric-Guérin, Hélène / Stanke-Labesque, Françoise

Forensic science international

2023 Volume 352, Page(s) 111835

Abstract: Background: Driving under the influence of drugs (DUID) is a risk factor for traffic accidents. The testing of oral fluid by roadside immunochromatography and laboratory-confirmed chromatography coupled to mass spectrometry (LC-MS/MS) analysis to detect ...

Abstract	Background: Driving under the influence of drugs (DUID) is a risk factor for traffic accidents. The testing of oral fluid by roadside immunochromatography and laboratory-confirmed chromatography coupled to mass spectrometry (LC-MS/MS) analysis to detect drug abuse has increased in France. The aim of this study was to describe the trends observed in drivers testing positive for illicit drugs in oral fluid and to investigate the concordance between the two analytical methods used. Methods: We received for confirmation 3051 oral fluid samples from drivers who had tested positive at the roadside with a Drugwipe-5S® device between 2018 and 2021 around Grenoble, France. Samples were collected with FLOQSwab® and analyzed by LC-MS/MS (THC, amphetamine, methamphetamine, MDMA and MDA, MDEA, cocaine and benzoylecgonine, morphine and 6-monoacetylmorphine) at Grenoble Alpes University Hospital, France. Binomial logistic regression was performed to evaluate consumption trends. Results: Most of the drivers were men (93.2%), with a median age of 26 years (range: 14-66 years). Cannabis (94.6%) cocaine (17.5%) and MDMA (2.5%) were the drugs most frequently detected. Poly-drug use was observed in 17.3% of drivers and involved cannabis and cocaine in 85.3% of these drivers. Poly-drug use was more frequent among drivers over the age of 32 years (OR, 3.48; 95% CI, 2.59-4.68; p ≤ .001), as was cocaine use (OR, 5.15; 95% CI, 3.75-7.08; p ≤ .001). The frequency of positive tests for amphetamines was higher in women than in men (OR, 2.53; 95% CI, 1.50-4.27; p ≤ .001). The positive predictive value of Drugwipe-5S was 98.2% for cannabis, 22.6% for amphetamines, 75.4% for cocaine and 17.3% for opiates. At least one discrepancy between Drugwipe-5S® and LC-MS/MS results was observed for 22.3% of the samples tested. Conclusion: We report recent trends for drivers testing positive for illicit drugs in oral fluid in France. Cannabis was the most prevalent drug of abuse identified, suggesting that a general prevention program might be useful. Our results also highlight the need for LC-MS/MS confirmation when screening oral fluid for drugs of abuse.
MeSH term(s)	Male ; Humans ; Female ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Chromatography, Liquid ; N-Methyl-3,4-methylenedioxyamphetamine/analysis ; Tandem Mass Spectrometry ; Substance-Related Disorders/diagnosis ; Substance-Related Disorders/epidemiology ; Illicit Drugs/analysis ; Cocaine/analysis ; Hallucinogens/analysis ; Amphetamine/analysis ; Cannabinoid Receptor Agonists/analysis ; Substance Abuse Detection/methods ; Saliva/chemistry ; Automobile Driving
Chemical Substances	N-Methyl-3,4-methylenedioxyamphetamine (KE1SEN21RM) ; Illicit Drugs ; Cocaine (I5Y540LHVR) ; Hallucinogens ; Amphetamine (CK833KGX7E) ; Cannabinoid Receptor Agonists
Language	English
Publishing date	2023-09-21
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	424042-x
ISSN	1872-6283 ; 0379-0738
ISSN (online)	1872-6283
ISSN	0379-0738
DOI	10.1016/j.forsciint.2023.111835
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Article ; Online: Smartphone swabs as an emerging tool for toxicology testing: a proof-of-concept study in a nightclub.

Willeman, Théo / Grunwald, Justine / Manceau, Marc / Lapierre, Frédéric / Krebs-Drouot, Lila / Boudin, Coralie / Scolan, Virginie / Eysseric-Guerin, Hélène / Stanke-Labesque, Françoise / Revol, Bruno

Clinical chemistry and laboratory medicine

2024

Abstract: Objectives: Smartphones have become everyday objects on which the accumulation of fingerprints is significant. In addition, a large proportion of the population regularly uses a smartphone, especially younger people. The objective of this study was to ... ...

Abstract	Objectives: Smartphones have become everyday objects on which the accumulation of fingerprints is significant. In addition, a large proportion of the population regularly uses a smartphone, especially younger people. The objective of this study was to evaluate smartphones as a new matrix for toxico-epidemiology. Methods: This study was conducted during two separate events (techno and trance) at an electronic music nightclub in Grenoble, France. Data on reported drug use and whether drugs were snorted directly from the surface of the smartphone were collected using an anonymous questionnaire completed voluntarily by drug users. Then, a dry swab was rubbed for 20 s on all sides of the smartphone. The extract was analyzed by liquid chromatography coupled to tandem mass spectrometry on a Xevo TQ-XS system (Waters). Results: In total, 122 swabs from 122 drug users were collected. The three main drugs identified were MDMA (n=83), cocaine (n=59), and THC (n=51). Based on declarative data, sensitivity ranged from 73 to 97.2 % and specificity from 71.8 to 88.1 % for MDMA, cocaine, and THC. Other substances were identified such as cocaine adulterants, ketamine, amphetamine, LSD, methamphetamine, CBD, DMT, heroin, mescaline, and several NPS. Numerous medications were also identified, such as antidepressants, anxiolytics, hypnotics, and painkillers. Different use patterns were identified between the two events. Conclusions: This proof-of-concept study on 122 subjects shows that smartphone swab analysis could provide a useful and complementary tool for drug testing, especially for harm-reduction programs and toxico-epidemiolgy studies, with acceptable test performance, despite declarative data.
Language	English
Publishing date	2024-04-05
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2024-0242
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Article ; Online: Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.

Stanke-Labesque, Françoise / Gautier-Veyret, Elodie / Chhun, Stephanie / Guilhaumou, Romain

Pharmacology & therapeutics

2020 Volume 215, Page(s) 107627

Abstract: Inflammation is an evolutionary process that allows survival against acute infection or injury. Inflammation is also a pathophysiological condition shared by numerous chronic diseases. In addition, inflammation modulates important drug-metabolizing ... ...

Abstract	Inflammation is an evolutionary process that allows survival against acute infection or injury. Inflammation is also a pathophysiological condition shared by numerous chronic diseases. In addition, inflammation modulates important drug-metabolizing enzymes and transporters (DMETs), thus contributing to intra- and interindividual variability of drug exposure. A better knowledge of the impact of inflammation on drug metabolism and its related clinical consequences would help to personalize drug treatment. Here, we summarize the kinetics of inflammatory mediators and the underlying transcriptional and post-transcriptional mechanisms by which they contribute to the inhibition of important DMETs. We also present an updated overview of the effect of inflammation on the pharmacokinetic parameters of most of the drugs that are DMET substrates, for which therapeutic drug monitoring is recommended. Furthermore, we provide opinions on how to integrate the inflammatory status into pharmacogenetics, therapeutic drug monitoring, and population pharmacokinetic strategies to improve the personalization of drug treatment for each patient.
MeSH term(s)	Animals ; Drug Monitoring ; Humans ; Inflammation/physiopathology ; Inflammation Mediators/metabolism ; Membrane Transport Proteins/metabolism ; Pharmaceutical Preparations/metabolism ; Pharmacogenetics ; Precision Medicine
Chemical Substances	Inflammation Mediators ; Membrane Transport Proteins ; Pharmaceutical Preparations
Keywords	covid19
Language	English
Publishing date	2020-07-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	194735-7
ISSN	1879-016X ; 0163-7258
ISSN (online)	1879-016X
ISSN	0163-7258
DOI	10.1016/j.pharmthera.2020.107627
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Article ; Online: A simple and easy-to-perform liquid chromatography-mass spectrometry method for the quantification of tacrolimus and its metabolites in human whole blood. Application to the determination of metabolic ratios in kidney transplant patients.

Chavant, Anaëlle / Jourdil, Jean-François / Jouve, Thomas / Christians, Uwe / Fonrose, Xavier / Stanke-Labesque, Françoise

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences

2021 Volume 1173, Page(s) 122698

Abstract: Tacrolimus is the cornerstone of immunosuppressive therapy in solid organ transplantation and its blood concentrations are routinely monitored. Tacrolimus is extensively metabolized into metabolites that are supposed to be nephrotoxic. Yet, few ... ...

Abstract	Tacrolimus is the cornerstone of immunosuppressive therapy in solid organ transplantation and its blood concentrations are routinely monitored. Tacrolimus is extensively metabolized into metabolites that are supposed to be nephrotoxic. Yet, few analytical methods have been described to simultaneously quantify tacrolimus and its main metabolites. We developed and validated a simple liquid chromatography-mass spectrometry method for the quantification of tacrolimus and its three desmethylated metabolites, 13-O, 15-O, and 31-O-desmethylated tacrolimus (M-I, M-III, and M-II respectively) in human whole blood. Protein precipitation of 50 µL of whole blood with 100 µL methanol and zinc sulfate was used as a single-extraction procedure. Tacrolimus and its metabolites were quantified using electrospray ionization-triple quadrupole mass spectrometry in combination with selected reaction monitoring detection in the positive ionization mode. The method was validated following FDA recommendations. This method was precise (intra- and inter-assay coefficients of variation: 2.88-7.81% and 3.96-12.10% for low and high levels of internal quality controls, respectively) and accurate (intra- and inter-assay biases: -1.67-10.30%, and -0.77--9.36%, respectively). In adult kidney transplant patients who were treated with tacrolimus prolonged release formulation, the median (10
Language	English
Publishing date	2021-04-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1180823-8
ISSN	1873-376X ; 0378-4347 ; 1570-0232 ; 1387-2273
ISSN (online)	1873-376X
ISSN	0378-4347 ; 1570-0232 ; 1387-2273
DOI	10.1016/j.jchromb.2021.122698
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