-
1.
Potential drug-drug interactions when managing status epilepticus patients in intensive care: A cohort study.
Le Roux, C, Destère, A, Hervy, S, Lloret-Linares, C, Reignier, J, Caillet, P, Jolliet, P, Mégarbane, B, Boels, D
British journal of clinical pharmacology. 2022;(5):2408-2418
-
-
Free full text
-
Abstract
AIMS: The risk for drug-drug interactions (DDIs) associated with antiseizure drugs (ASDs) used to manage status epilepticus (SE) patients in the intensive care unit (ICU) has been poorly investigated. We aimed to quantify and describe those potential DDIs and determine SE patient risk profiles. METHODS We conducted an observational bi-centric cohort study including all SE patients admitted to the ICU in the period 2016-2020. RESULTS Overall, 431 SE patients were included and 5504 potential DDIs were identified including 1772 DDIs (33%) between ASDs, 2610 DDIs (47%) between ASDs and previous usual treatments (PUTs), and 1067 DDIs (20%) between ASDs and ICU treatments (ICUTs). DDIs were moderate (n = 4871), major (n = 562) or severe (n = 16). All patients exhibited potential DDIs, which were major-to-severe DDIs in 47% of the cases. DDIs were pharmacokinetic (n = 1972, 36%), mostly involving cytochrome P450 modulators, and pharmacodynamic (n = 3477, 64%), mainly leading to increased sedation. ASD/PUT DDIs were the most frequent and severe. Age, PUT and ASD drug numbers and length of ICU stay were significantly associated with increased DDI number. We identified four SE patient profiles with different DDI risks and outcomes including (1) epileptic or brain trauma patients, (2) withdrawal syndrome patients, (3) older patients with comorbidities and (4) self-poisoned patients with psychiatric disorders and/or past epilepsy. CONCLUSION SE patients are subject to potential DDIs between ASDs, ASD/PUT and ASD/ICUT. Major-to-severe DDIs mostly occur between ASDs and PUTs. Physicians should pay attention to SE patient characteristics and history to limit DDI numbers and prevent their consequences.
-
2.
Glucocorticoids dosing in obese subjects: A systematic review.
Delaleu, J, Destere, A, Hachon, L, Declèves, X, Lloret-Linares, C
Therapie. 2019;(4):451-458
Abstract
Glucocorticoids (GCs) are amongst the most widely used and effective treatments to control inflammatory and autoimmune diseases. In obese subjects, drug dosing adjusted by body weight is problematic, all the more so as patients are at higher risk of GC metabolic side effects. We propose here to describe the determinants of drug pharmacokinetics (PK) in obese subjects and GC pharmacology, and to identify the existing PK studies that may help discussing the best size descriptor for GC dosing in obese subjects. A clinician and a pharmacist screened PubMed using the MeSH Terms: "glucocorticoids" OR "steroidal agents" AND "pharmacokinetics" AND "obesity" OR "overweight". The search was limited to the publications written in English language and to those performed in humans. A systematic search using the MeSH terms was performed until August 31st, 2017. Only three such PK studies have been published so far that compare dexamethasone, prednisolone and methylprednisolone in obese and normal weight subjects. The studies concur that GC partially distribute in the excess of body weight and that adjustment by total body weight (TBW) or by body weight (BW) excess would increase the initial plasma GC concentration after a loading dose and would thus be inappropriate. Contradictory results are observed regarding GC exposure or clearance according to the GC studied. Behind this overwhelming lack of conclusive evidence for adjusting GC by body weight, further PK studies are clearly needed for guiding their dosing. Furthermore, studies demonstrated an increased sensibility to GC, even when GC exposure was reduced, suggesting that adjustment by body weight may not only be unnecessary but also dangerous.
-
3.
CYP450 activities before and after Roux-en-Y gastric bypass: correlation with their intestinal and liver content.
Lloret-Linares, C, Daali, Y, Abbara, C, Carette, C, Bouillot, JL, Vicaut, E, Czernichow, S, Declèves, X
Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. 2019;(8):1299-1310
Abstract
BACKGROUND Several anatomic and physiologic changes occur after Roux-en-Y gastric bypass (RYGB) and its associated weight loss. At present, no single unified model can predict changes in drug metabolism associated with either RYGB surgery or weight loss. OBJECTIVE The aim of this longitudinal human study was to measure the activity of the 5 most important Cytochrome P450 (CYP) involved in drug metabolism in patients with obesity before and after RYGB. Jejunal and liver biopsies obtained during bariatric surgery were used to measure CYP amount, and correlation between jejunal and hepatic content was estimated. SETTING French university hospital. METHODS Eleven volunteers with a mean body mass index of 44.1 (39.4-50.0) kg/m2 participated in the study. CYP1 A2, CYP2 C9, CYP2 C19, CYP2 D6, and CYP3 A4/A5 activities were measured with a cocktail approach before surgery (visit 1), 5 to 8 weeks after surgery (visit 2), and 25 to 30 weeks after surgery (visit 3). RESULTS CYP3 A4/A5 and CYP2 C9 metabolic ratios were transitorily and significantly increased immediately after surgery (visit 2 versus 1). RYGB procedure does not lead to significant change in CYP activity 25 to 30 weeks after surgery (visit 3 versus 1). Samples obtained during surgery showed significant correlation between intestinal and liver contents of CYP2 C9 and CYP3 A4/A5. Except for liver CYP1 A2 content, CYP metabolic activities were not correlated to their intestinal or liver contents. CONCLUSIONS This study showed that RYGB does not lead to a significant change in CYP activity 25 to 30 weeks after surgery. However, CYP3 A4/A5 and CYP2 C9 activities were transitorily and significantly increased in the immediate postoperative context (<1 mo), representing a situation at risk of reduced drug exposure for several drugs that have a narrow therapeutic window. In addition, considering high interindividual variability in liver contents and activity of CYP3 A4 and CYP2 C9, patients receiving drugs highly metabolized by these 2 CYPs should be closely monitored in the immediate postoperative period.
-
4.
Changes in Alcohol Use after Metabolic and Bariatric Surgery: Predictors and Mechanisms.
Ivezaj, V, Benoit, SC, Davis, J, Engel, S, Lloret-Linares, C, Mitchell, JE, Pepino, MY, Rogers, AM, Steffen, K, Sogg, S
Current psychiatry reports. 2019;(9):85
-
-
Free full text
-
Abstract
PURPOSE OF REVIEW This review synthesized the literature on predictors and mechanisms of post-bariatric alcohol problems, in order to guide future research on prevention and treatment targets. RECENT FINDINGS Consistent evidence suggests an elevated risk of developing problems with alcohol following bariatric surgery. While there is a paucity of empirical data on predictors of problematic alcohol use after bariatric surgery, being male, a younger age, smoking, regular alcohol consumption, pre-surgical alcohol use disorder, and a lower sense of belonging have predicted alcohol misuse post-operatively. This review synthesizes potential mechanisms including specific bariatric surgical procedures, peptides and reinforcement/reward pathways, pharmacokinetics, and genetic influences. Finally, potential misperceptions regarding mechanisms are explored. Certain bariatric procedures elevate the risk of alcohol misuse post-operatively. Future research should serve to elucidate the complexities of reward signaling, genetically mediated mechanisms, and pharmacokinetics in relation to alcohol use across gender and developmental period by surgery type.
-
5.
Binge eating behaviours in bipolar disorders.
Boulanger, H, Tebeka, S, Girod, C, Lloret-Linares, C, Meheust, J, Scott, J, Guillaume, S, Courtet, P, Bellivier, F, Delavest, M
Journal of affective disorders. 2018;225:482-488
-
-
-
Plain language summary
Bipolar disorder (BD) is a mental health condition that is often found alongside other health conditions including eating disorders such as anorexia nervosa and bulimia nervosa. More recently, it has been also associated with binge eating disorder (BED) which is characterised by frequent episodes of binge eating (BE), often involving a lot of food in a short space of time and a loss of control. It is estimated that 15-17% of people with BD binge eat, compared to 2-5% of the general population. The added burden of binge eating for those with BD includes increased mood instability, anxiety, additions, episodes of psychosis, obesity, suicide, and cardiovascular disease. This study aimed to explore the prevalence and characteristics of binge eating behaviour in those with BD attending BD clinics in France. Individuals with BD with and without binge eating behaviour were compared on factors including demographics and behavioural elements like eating habits. 145 outpatients with BD were included and assessed for binge eating using the Binge Eating Scale. 19% of BD patients were found to binge eat and was more likely in those with a shorter duration of BD, being emotional reactive and having higher levels of anxiety. However, the small sample meant it was hard to assess any differences in personality characteristics like impulsivity.
Abstract
BACKGROUND Recent research, especially from the USA, suggests that comorbid binge eating (BE) behaviour and BE disorder are frequent in individuals with Bipolar Disorder (BD). Although basic clinical associations between BD and BE have been investigated, less is known about psychological or temperamental dimensions and qualitative aspects of eating habits. In a French cohort of patients with BD, we investigated the prevalence of BE behaviour and any associations with illness characteristics, anxiety, impulsivity, emotional regulation and eating habits. METHODS 145 outpatients with BD (I and II) were assessed for the presence of BE behaviour using the Binge Eating Scale (BES). Characteristics identified in univariate analyses as differentiating BD cases with and without BE behaviour were then included in a backward stepwise logistic regression (BSLR) model. RESULTS In this sample, 18.6% of BD patients met criteria for BE behaviour. Multivariate analysis (BSLR) indicated that shorter duration of BD, and higher levels of anxiety and emotional reactivity were observed in BD with compared to BD without BE behaviour. LIMITATIONS Relatively small sample referred to specialist BD clinics and cross-sectional evaluation meant that it was not possible to differentiate between state and trait levels of impulsivity, emotional instability and disinhibition. These dimensions may also overlap with mood symptoms. CONCLUSION BE behaviour is common in females and males with BD. Emotional dysregulation and anxiety may represent important shared vulnerability factors for worse outcome of BD and increased likelihood of BE behaviour.
-
6.
Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort?
Mouly, S, Lloret-Linares, C, Sellier, PO, Sene, D, Bergmann, JF
Pharmacological research. 2017;:82-92
Abstract
An interaction of drug with food, herbs, and dietary supplements is usually the consequence of a physical, chemical or physiologic relationship between a drug and a product consumed as food, nutritional supplement or over-the-counter medicinal plant. The current educational review aims at reminding to the prescribing physicians that the most clinically relevant drug-food interactions may not be strictly limited to those with grapefruit juice and with the Saint John's Wort herbal extract and may be responsible for changes in drug plasma concentrations, which in turn decrease efficacy or led to sometimes life-threatening toxicity. Common situations handled in clinical practice such as aging, concomitant medications, transplant recipients, patients with cancer, malnutrition, HIV infection and those receiving enteral or parenteral feeding may be at increased risk of drug-food or drug-herb interactions. Medications with narrow therapeutic index or potential life-threatening toxicity, e.g., the non-steroidal anti-inflammatory drugs, opioid analgesics, cardiovascular medications, warfarin, anticancer drugs and immunosuppressants may be at risk of significant drug-food interactions to occur. Despite the fact that considerable effort has been achieved to increase patient' and doctor's information and ability to anticipate their occurrence and consequences in clinical practice, a thorough and detailed health history and dietary recall are essential for identifying potential problems in order to optimize patient prescriptions and drug dosing on an individual basis as well as to increase the treatment risk/benefit ratio.
-
7.
RYGB and Drug Disposition: How to Do Better? Analysis of Pharmacokinetic Studies and Recommendations for Clinical Practice.
Hachon, L, Declèves, X, Faucher, P, Carette, C, Lloret-Linares, C
Obesity surgery. 2017;(4):1076-1090
Abstract
An important issue in the follow-up of patients with bariatric surgery remains to determine whether their therapeutic management should be different after surgery. In this article, we first reviewed all pharmacokinetic studies involving at least four subjects who underwent the Roux-en-Y gastric bypass (RYGB) bariatric surgery. Twenty-five publications were selected and, overall, 25 drugs were studied. Drug solubility and permeability parameters for each drug were defined using different parameters or classifications. Increased rates of oral drug absorption were predominantly observed. Conversely, drug exposure differed from one drug to another. Considering the galenic formulation and the Biopharmaceutics Classification System (BCS) class may help the prediction of oral drug exposure outcome after RYGB. We propose a strategy aiming to guide prescription and drug monitoring in patients with RYGB. But further research is clearly needed due to the unique characteristics of the bariatric population. Priority should be given to drugs that do not have clinical or biological surrogates for dose adaptation.
-
8.
Absorption and efficacy of acetylsalicylic acid in patients with short bowel syndrome.
Faye, E, Drouet, L, De Raucourt, E, Green, A, Bal-Dit-Sollier, C, Boudaoud, L, Corcos, O, Bergmann, JF, Joly, F, Lloret-Linares, C
The Annals of pharmacotherapy. 2014;(6):705-10
Abstract
BACKGROUND The patients with a short bowel (SB) frequently require antiplatelet therapy. Resection of the bowel is likely to modify the absorption and first-pass effect of drugs. No data on the absorption and efficacy of the cardiovascular dose of aspirin (75-160 mg) in these patients have been published. OBJECTIVE To evaluate the efficacy of a low dose of aspirin in patients with SB caused by mesenteric ischemia. METHODS The efficacy of a low dose of aspirin was assessed in 10 consecutive SB patients, both 1 hour and 24 hours after administration (peak and trough value, respectively). The primary criterion was the inhibition of platelet aggregation, as assessed by light transmission aggregometry, triggered with 0.5 mg/mL arachidonic acid. Biological efficacy of aspirin was also evaluated by serum thromboxane B2 value and by platelet function analyzer-100. RESULTS At its peak value, aspirin had the expected efficacy, as demonstrated both by light transmission aggregometry and the other methods. However, 24 hours after administration, as many as 30% of patients had lost the pharmacological efficacy of their aspirin. CONCLUSION We show for the first time that with at least 30 cm of small intestine, all patients with SB absorb sufficient oral aspirin in a cardiovascular dose to rapidly exert the expected level of antiplatelet activity. But given only once daily, aspirin does not provide stable 24-hour antiplatelet protection in 30% of patients, because of increased platelet turnover, as usually observed in patients with extensive vascular pathology, diabetes, or inflammation.
-
9.
Effect of weight-reducing agents on glycaemic parameters and progression to Type 2 diabetes: a review.
Lloret-Linares, C, Greenfield, JR, Czernichow, S
Diabetic medicine : a journal of the British Diabetic Association. 2008;(10):1142-50
Abstract
Weight loss is associated with improvements in glycaemic control and cardiovascular disease risk factors. However, in the diabetic population, weight management is more challenging, in part because of the weight-promoting effects of the majority of glucose-lowering therapies. This review summarizes evidence from 23 placebo-controlled randomized trials, of at least 1 year duration, on the effects of drugs promoting weight loss (orlistat, sibutramine and rimonabant) on glycaemic variables, diabetes incidence and diabetes control. Fifteen studies of non-diabetic subjects were found, eight of which included a longer treatment period. Eight studies in diabetic patients were reviewed. In non-diabetic subjects, weight loss agents led to a significant improvement in fasting glucose, fasting insulin and insulin resistance. In the diabetic population, glycated haemoglobin decreased by 0.28-1.1% with orlistat and 0.6% with sibutramine and rimonabant. Orlistat reduces progression to diabetes in patients with glucose intolerance treated for 4 years (risk reduction of 45%). In summary, despite leading to only modest weight loss after 12 months, agents promoting weight loss have beneficial effects on glycaemic parameters, glycaemic control and progression to diabetes. These additional benefits of weight loss agents need to be highlighted in order to increase their judicious use in clinical practice, although this may be limited by their well-known adverse side effects. The longer-term safety of these agents beyond a few years is yet to be established.