Caroline Solas

Caroline Solas
Assistance Publique Hôpitaux de Marseille | APHM · Pharmacology and Toxicology

Pharm D, Ph D

About

151
Publications
7,579
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2,293
Citations
Citations since 2017
76 Research Items
1263 Citations
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20172018201920202021202220230100200300400

Publications

Publications (151)
Article
In the last two years, the number of shops selling CBD‐rich THC‐deprived cannabis flowers (CrTd) has increased considerably in France as in many European countries. The objective of this study was to determine the actual composition of the samples sold in these stores, and to discuss regulatory consequences that may affect users. Samples were provi...
Article
Aim To present a case series of cocaine pediatric poisoning. Cocaine pediatric poisonings are rare but lead to the most serious clinical pictures among the pediatric poisonings (Armenian, J Emerge Med, 2007, 52, 825–32). The most frequently described symptoms are tachycardia, convulsions and loss of consciousness (Dinnies, Am J Dis Child, 1990, 144...
Article
Aim The continual emergence of new psychoactive substances remains a global health issue. We reported a case of serotoninergic syndrome following the consumption of 3,4-methylenedioxy-α-pyrrolidinohexanophenone (MDPHP) and 25H-NBOH documented by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Method/Case A 23-year-old...
Article
Full-text available
The COVID-19 pandemic has exemplified that rigorous evaluation in large animal models is key for translation from promising in vitro results to successful clinical implementation. Among the drugs that have been largely tested in clinical trials but failed so far to bring clear evidence of clinical efficacy is favipiravir, a nucleoside analogue with...
Article
Measuring uracil (U) levels in plasma is a convenient surrogate to establish DPD status in patients scheduled with 5‐fluorouracil (5‐FU) or capecitabine. To what extent renal impairment could impact on U levels and thus be a confounding factor is a rising concern. Here, we report the case of a cancer patient with severe renal impairment scheduled f...
Article
Full-text available
Background :To address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy. Methods: In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide ag...
Article
Full-text available
Purpose Better understanding of pharmacokinetics of oral vinorelbine (VNR) in children would help predicting drug exposure and, beyond, clinical outcome. Here, we have characterized the population pharmacokinetics of oral VNR and studied the factors likely to explain the variability observed in VNR exposure among young patients. Design/methods We...
Poster
Objectives:Defining a safe and effective dose in children is one of the biggest challenges in pediatric drug development. Pharmacometric tools are proposed as powerful quantitative techniques to leverage and integrate the collected data from pediatric clinical trials. Here we demonstrate and discuss the applications of nonlinear mixed effects (NLME...
Article
Objectives.- Nirmatrelvir in association with ritonavir (PAXLOVID™, Pfizer) is an antiviral agent targeting the 3-chymotrypsin–like cysteine protease enzyme (3C-like protease or Mpro) which is a key enzyme of the viral cycle of the SARS-CoV-2. This combination with a well-known pharmacokinetic enhancer leads to a high risk for drug-drug interaction...
Article
Full-text available
During the SARS-CoV-2 pandemic, hydroxychloroquine (HCQ), was among the first drugs to be tested due to demonstrated in vitro antiviral activity against SARS-CoV-2. Pharmacokinetic variability was expected due to the frequent comorbidities and pathophysiological modifications observed in severe COVID-19 patients hospitalized in intensive care units...
Article
Full-text available
People living with HIV (PLWH) with advanced immunosuppression who initiate antiretroviral therapy (ART) are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS). Although ART is responsible for AIDS- associated Kaposi sarcoma (KS) improvement and resolution, new onset (unmasking KS-IRIS) or sudden progression of pr...
Article
Full-text available
The aim of this study was to develop and to validate a toxicological untargeted screening relying on LC-HRMS in meconium including the detection of the four main classes of drugs of abuse (DoA; amphetamines, cannabinoids, opioids and cocaine). The method was then applied to 29 real samples. Analyses were performed with a liquid chromatography syste...
Preprint
Full-text available
To address the emergence of SARS-CoV-2, multiple clinical trials in humans were rapidly started, including those involving an oral treatment by nitazoxanide, despite no or limited pre-clinical evidence of antiviral efficacy. In this work, we present a complete pre-clinical evaluation of the antiviral activity of nitazoxanide against SARS-CoV-2. Fir...
Article
Résumé Les intoxications pédiatriques au diéthylamide de l’acide lysergique (LSD) sont rares mais potentiellement graves, elles peuvent engendrer une expérience perturbante pour le développement psychologique de l’enfant. Le LSD est un puissant hallucinogène initialement développé comme traitement pour les maladies psychiatriques et principalement...
Article
Full-text available
Since the advent of highly effective combined antiretroviral treatment (cART), and with the implementation of large HIV testing programs and universal access to cART, the burden of AIDS-related comorbidities has dramatically decreased over time. The incidence of Kaposi’s sarcoma (SK), strongly associated with HIV replication and CD4 immunosuppressi...
Article
Full-text available
Drug repositioning has been used extensively since the beginning of the COVID-19 pandemic in an attempt to identify antiviral molecules for use in human therapeutics. Hydroxychloroquine and azithromycin have shown inhibitory activity against SARS-CoV-2 replication in different cell lines. Based on such in vitro data and despite the weakness of prec...
Article
Aim: There is a crucial need for pharmacokinetic (PK) data of oral vinorelbine (VNR) in pediatric population. The aim of this work was to assess the PK profile of orally administered VNR in children with recurrent/progressive primary low-grade glioma (LGG). Methods: A multicentric, open-label, single-arm intervention phase II study was conducted...
Conference Paper
Objectifs L’objectif de ce travail a été de développer une méthode de criblage toxicologique en chromatographie gazeuse couplée à spectrométrie de masse (CG-SM), méthode de référence dans le domaine de la toxicologie hospitalière [1] en utilisant le logiciel de retraitement MassHunter Unkown Analysis (MHUA), applicable en routine pour des échantill...
Conference Paper
Objectifs Bien que l’usage récréatif du cannabis en France soit illégal, la population française (18–75 ans) est au premier rang européen en termes d’expérimentation (45 %), et la région Provence-Alpes-Côte d’Azur est de loin la première du classement national (54 %). Cette banalisation de l’usage du cannabis expose les enfants à un risque plus imp...
Article
Objectives HIV-coinfected patients experience higher incidences of non-liver-related cancers than HCV-monoinfected patients. Chronic inflammation, immunosuppression, but also higher tobacco or alcohol consumption and metabolic dysregulation could explain this higher risk. We aimed to estimate the direct, indirect and total effects of HIV coinfectio...
Article
Introduction People living with HIV (PLWHIV) are at a higher risk of cancer compared to the general population. With improved cancer treatments and the increased life expectancy of PLWHIV, the incidence of second cancers is also expected to increase. Methods We reviewed the cases of PLWHIV with cancer that have been presented to the CANCERVIH nati...
Article
Full-text available
Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has...
Article
Résumé L’objectif de ce travail est d’évaluer une méthode de criblage toxicologique en chromatographie gazeuse couplée à la spectrométrie de masse (CG-SM) dans le plasma et dans l’urine, en utilisant le logiciel de retraitement MassHunter Unkown Analysis (MHUA). Les résultats sont comparés à ceux obtenus en CG-SM avec le logiciel AMDIS et en chroma...
Article
France is the country with the highest prevalence of cannabis use in Europe, despite the fact that cannabis has not been legalized. This prevalence is still increasing along with THC content in cannabis products. In the meantime, unintentional cannabis poisoning by ingestion in toddlers is constantly rising. The aim of this study was to document ch...
Article
Full-text available
Despite no or limited pre-clinical evidence, repurposed drugs are massively evaluated in clinical trials to palliate the lack of antiviral molecules against SARS-CoV-2. Here we use a Syrian hamster model to assess the antiviral efficacy of favipiravir, understand its mechanism of action and determine its pharmacokinetics. When treatment is initiate...
Article
Full-text available
Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large burst size (>10 ⁴ virus) and a within-host reproduc...
Article
Résumé Le dépistage de l’infection par le VIH est recommandé lors du bilan initial de tout cancer, celui de l’hépatite B et C en raison d’un risque de réactivation avec certains anticancéreux. Il s’agit d’une étude prospective transversale. Les objectifs étaient d’évaluer les pratiques de dépistage chez des patients atteints de cancer et la satisfa...
Article
Full-text available
Boffito et al. recalled the critical importance to correctly interpret protein binding. Changes of lopinavir pharmacokinetics in COVID-19 are a perfect illustration. Indeed, several studies described that total lopinavir plasma concentrations were considerably higher in severe COVID-19 patients than those reported in HIV patients. These findings ha...
Article
Résumé Les intoxications au laurier rose (Nerium oleander) sont peu fréquentes mais sont graves. La plante contient un hétéroside cardiotonique, l’oléandrine, pouvant conduire au décès par arrêt cardiaque. Les auteurs présentent le cas d’une patiente âgée de 86 ans ayant tenté de mettre fin à ses jours en ingérant une infusion de feuilles de laurie...
Preprint
Full-text available
Following the emergence of SARS-CoV-2, the search for an effective and rapidly available treatment was initiated worldwide based on repurposing of available drugs. Previous reports described the antiviral activity of certain tyrosine kinase inhibitors (TKIs) targeting the Abelson kinase 2 against pathogenic coronaviruses. Imatinib, one of them, has...
Article
Therapeutic drug monitoring (TDM) of hydroxychloroquine has been recommended to optimize the treatment of COVID-19 patients. The authors describe an ultra-high-performance liquid chromatography tandem spectrometry ( UHPLC-MS/MS) method developed in a context of emergency, to analyze hydroxychloroquine (HCQ) in both human plasma and blood samples.Af...
Article
Full-text available
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effe...
Article
Full-text available
COVID-19 has rapidly become a pandemic for which no antiviral drug or vaccine is yet available2–4. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individuals worldwide but definitive...
Article
Full-text available
Background: Haemodialysis patients are at risk of developing severe forms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: coronavirus disease 2019 (COVID-19). In March 2020, hydroxychloroquine (HCQ) and azithromycin (AZI) were proposed as potential treatments of COVID-19, but with warnings concerning their possible toxic...
Preprint
Full-text available
Non-human primates infected with SARS-CoV-2 exhibit mild clinical signs. Here we used a mathematical model to characterize in detail the viral dynamics in 31 cynomolgus macaques infected with 10 ⁶ pfu of SARS-CoV-2 for which nasopharyngeal and tracheal viral load were frequently assessed. We identified that infected cells had a large daily viral pr...
Preprint
Full-text available
There is a need for safe and effective antiviral molecules with which to combat COVID-19 pandemics. Recently, in vitro inhibitory activity of favipiravir against SARS-CoV-2 was reported. Here, we used a Syrian hamster model to explore the pharmacokinetics of this molecule and its in vivo efficacy against SARS-CoV-2. Results revealed that high doses...
Article
Full-text available
In the context of the COVID-19 pandemic, several drugs have been repurposed as potential candidates for the treatment of COVID-19 infection. While preliminary choices were essentially based on in vitro potency, clinical translation into effective therapies may be challenging due to unfavorable in vivo pharmacokinetic properties at the doses chosen...
Article
Aims: The purpose of this study was to assess the antiviral activity of the rilpivirine/emtricitabine/tenofovir disoproxil fumarate combination and to describe the pharmacokinetics of rilpivirine and its association with resistance in clinical routine. Methods: A retrospective multicenter cohort study was performed in both naive and pre-treated...
Preprint
Full-text available
COVID-19 has become a pandemic that has caused over 200,000 deaths worldwide, with no antiviral drug or vaccine yet available. Several clinical studies are ongoing to evaluate the efficacy of repurposed drugs that have demonstrated antiviral efficacy in vitro. Among these candidates, hydroxychloroquine (HCQ) has been given to thousands of individua...
Article
We read with a great interest the paper by Du et Chen suggesting dosing regimen of favipiravir in COVID‐191. We would like to complement their observations with our PK/PD experience of favipiravir against Ebola virus (EBOV). The drug EC50 against EBOV and SARS‐CoV‐2 are 10‐60 µg/ml and 9.4 µg/ml4, respectively. However results obtained by our worki...
Article
Background In spite of recurrent and dramatic outbreaks, there are no therapeutics approved against Ebola virus disease. Favipiravir, a RNA polymerase inhibitor active against several RNA viruses, recently demonstrated significant but not complete protection in non-human primate model of Ebola virus disease. In this study, we assessed the benefit o...
Article
Full-text available
Detecting patients with DPD deficiency is becoming a major concern in clinical oncology. Monitoring physiological plasma uracil and/or plasma uracil‐to‐dihydrouracil metabolic ratio is a common surrogate frequently used to determine DPD phenotype without direct measurement of the enzymatic activity. With respect to the rising number of patients to...
Article
The HIV infection remains a serious public health concern in France and around the World. Cancers are frequent among people living with HIV (PLWH) and have become the leading cause of mortality among this population in France. Certain non-AIDS-defining cancers are much more common among PLWH, such as anal carcinoma, Hodgkin lymphoma, hepatocellular...
Article
Cabozantinib is a novel multi-target tyrosine kinase inhibitor recently approved in metastatic renal cell carcinoma (mRCC) leading to frequent severe toxicities requiring empirical dose reduction. Therapeutic drug monitoring (TDM) could help to predict the risk for severe toxicities by quickly detecting overexposed patients followed by prospective...
Article
Objective: Treatment recommendations for hepatitis C now make no distinction between HIV/HCV-coinfected and HCV-monoinfected patients. The largest challenge remained lack of effective models to eliminate HCV in people living with HIV. We report the results of a microelimination program evaluating the possibility of eradicating HCV in an HIV-outpat...
Article
Background: HIV-HCV co-infected patients are at high risk of metabolic complications and liver-related events, which are both associated with hepatic steatosis and its progressive form, non-alcoholic steatohepatitis (NASH), a known risk factor for mortality. The fatty liver index (FLI), a non-invasive steatosis biomarker, has recently drawn attent...
Article
In 21 cutaneous and/or visceral Kaposi's sarcoma cases, occurring in patients living with human immunodeficiency virus (HIV) who were on antiretroviral therapy with suppressed HIV viremia and high CD4 T cell counts, the efficacy of conventional chemotherapies was limited due to cumulative toxicities, comedications, and a lack of immune improvement.
Article
Purine analogs like aracytine (AraC) are a mainstay for treating acute myeloid leukemia (AML). There are marked differences in drug dosing and scheduling depending on the protocols when treating AML patients with AraC. Large inter-patient pharmacokinetics variability has been reported, and genetic polymorphisms affecting cytidine deaminase (CDA), t...
Article
Dihydropryimidine dehydrogenase (DPD) deficiency is a pharmacogenetic syndrome associated with severe or lethal toxicities with oral capecitabine. Usually, patients with history of 5-FU-based therapy with no signs for life-threatening toxicities are considered as not DPD-deficient individuals who can be safely treated next with capecitabine if requ...
Article
Background: Rilpivirine is widely prescribed in people living with HIV. Although trough plasma concentrations have been associated with virological response, the drug pharmacodynamics remain incompletely characterized. Objectives: To develop the first pharmacodynamic model of rilpivirine in order to establish the rilpivirine concentration-respon...
Chapter
Due to shared routes of transmission, prevalence of hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients is high.
Article
Introduction Le dépistage du VIH est recommandé lors du bilan initial de tout cancers, celui du VHB lors du recours à certaines immunothérapies en raison du risque de réactivation. La prévalence de troubles dysimmunitaires justifie le dépistage du VHC avant le recours à une immunothérapie. Cette enquête a pour objectif d’évaluer les pratiques de dé...
Article
Full-text available
Aim: To describe factors associated with treatment failure and frequency of resistance-associated substitutions (RAS). Methods: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfected patients starting a first direct-acting antiviral (DAA) regimen before February 2016 and included in the French ANRS CO13 HEPAVIH cohort were eligibl...
Article
Full-text available
Despite several clinical trials implemented, no antiviral drug could demonstrate efficacy against Ebola virus. In non-human primates, early initiation of polymerase inhibitors favipiravir and remdesivir improves survival, but whether they could be effective in patients is unknown. Here we analyze the impact of antiviral therapy by using a mathemati...
Article
The advent of direct-acting antiviral agents (DAAs) has transformed the hepatitis C virus (HCV) therapeutic landscape in terms of efficacy and safety, with a cure rate of more than 90%. However, an important potential for drug-drug interactions (DDIs) is expected with these combinations, particularly in patients with other comorbidities (e.g. HIV c...
Article
Full-text available
Purpose: Rilpivirine, prescribed for the treatment of HIV infection, presents an important inter-individual pharmacokinetic variability. We aimed to determine population pharmacokinetic parameters of rilpivirine in adult HIV-infected patients and quantify their inter-individual variability. Methods: We conducted a multicenter, retrospective, and...
Article
Résumé L’amélioration de l’espérance de vie des personnes vivant avec le VIH (PVVIH) depuis l’avènement des thérapies antirétrovirales combinées s’accompagne d’une modification des causes de décès chez ces patients. Le cancer, qu’il soit classant ou non classant SIDA, est devenu la première cause de mortalité chez les personnes vivant avec le VIH,...
Article
Background: The aim of this study was to investigate the correlation between 7-hydroxymethotrexate (7-OHMTX) and creatinine and to evaluate the predictive value of 7-OHMTX levels on delayed elimination at 24 and 48 hours. In addition, differences in methotrexate (MTX), 7-OHMTX levels, and MTX metabolism using the ratio MTX/7-OHMTX were determined...
Article
We evaluate the impact of ledipasvir on both tenofovir plasma trough concentration (Ctrough ) and estimated glomerular renal function (eGFR) in HIV-HCV co-infected patients receiving a tenofovir(TDF)-based antiretroviral regimen and treated with ledipasvir/sofosbuvir. Twenty-six patients [81% male, median age: 51years; HCV genotype 1(75%)/4(15%)] w...
Article
Background: Tenofovir disoproxil fumarate (TDF)-based regimen is a treatment option for HIV-infected patients. TDF dose adjustment is recommended in patients with impaired renal function. We assessed the impact of TDF dose adjustment on renal function and tenofovir trough concentration. Methods: Fourteen HIV patients for whom TDF dose was adjust...
Article
Background: We aimed to determine the impact of inosine triphosphatase (ITPA) deficiency on ribavirin (RBV) induced anemia in HIV-HCV co-infected patients receiving a triple therapy including the hematotoxic direct-acting antiviral agent boceprevir (BOC). Methods: Patients of the ANRS HC27 BocepreVIH study were genotyped for 2 ITPA Single nucleo...
Article
Objectives: Ribavirin (RBV) induced anemia may be influenced by host genetic factors affecting RBV transport (SLC) or metabolism (ITPA) as already reported. We investigated the influence of single nucleotide polymorphisms (SNPs) on SLC genes on anemia, RBV trough concentration (Ctrough) and response in HIV-HCV co-infected patients receiving triple...
Article
Background: Scarce data exist on the efficacy and safety of the PEGylated-interferon/ribavirin/boceprevir regimen in HIV/HCV-coinfected patients who failed to respond to PEGylated-interferon/ribavirin treatment. Objectives: To evaluate the efficacy and safety of this drug regimen and the impact of the addition of boceprevir(BOC) on atazanavir (A...