Management of Pain Medication in Patients With a History of Bariatric Surgery: A Systematic Review.

Context: Obesity prevalence is persistently increasing worldwide. Among surgical therapeutic procedures, bypass surgery and sleeve gastrectomy have shown the best results regarding weight loss, prevention, and treatment of secondary complications. However, these surgeries are associated with an increased risk of malabsorption and metabolic changes that could further affect the pharmacokinetics of drugs.

Phenotyping Indices of CYP450 and P-Glycoprotein in Human Volunteers and in Patients Treated with Painkillers or Psychotropic Drugs.

Drug-metabolizing enzymes and drug transporters are key determinants of drug pharmacokinetics and response. The cocktail-based cytochrome P450 (CYP) and drug transporter phenotyping approach consists in the administration of multiple CYP or transporter-specific probe drugs to determine their activities simultaneously. Several drug cocktails have been developed over the past two decades in order to assess CYP450 activity in human subjects.

Cytochromes P450 and P-Glycoprotein Phenotypic Assessment to Optimize Psychotropic Pharmacotherapy: A Retrospective Analysis of Four Years of Practice in Psychiatry.

Altered cytochromes P450 enzymes (CYP) and P-glycoprotein transporter (P-gp) activity may explain variabilities in drug response. In this study, we analyzed four years of phenotypic assessments of CYP/P-gp activities to optimize pharmacotherapy in psychiatry. A low-dose probe cocktail was administered to evaluate CYP1A2, 2B6, 2D6, 2C9, 2C19, 3A4, and P-gp activities using the probe/metabolite concentration ratio in blood or the AUC.

Potential drug-drug interactions when managing status epilepticus patients in intensive care: A cohort study.

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.

Drug-induced meningitis: A review of the literature and comparison with an historical cohort of viral meningitis cases.

Background: Drug-induced aseptic meningitis (DIAM) is potentially insufficiently considered by clinician, being of rare etiology, with there being no previously published exhaustive study describing its clinical and biological features.

Methods: Two independent academic clinicians searched all the case reports of DIAM from 1995 until 15 April, 2017. The search was limited to studies performed in humans, published in English or French.

Evaluation of Phenotypic and Genotypic Variations of Drug Metabolising Enzymes and Transporters in Chronic Pain Patients Facing Adverse Drug Reactions or Non-Response to Analgesics: A Retrospective Study.

This retrospective study evaluates the link between an adverse drug reaction (ADR) or a non-response to treatment and cytochromes P450 (CYP), P-glycoprotein (P-gp) or catechol-O-methyltransferase (COMT) activity in patients taking analgesic drugs for chronic pain. Patients referred to a pain center for an ADR or a non-response to an analgesic drug between January 2005 and November 2014 were included. The genotype and/or phenotype was obtained for assessment of the CYPs, P-gp or COMT activities.

Changes in Alcohol Use after Metabolic and Bariatric Surgery: Predictors and Mechanisms.

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.

CYP450 activities before and after Roux-en-Y gastric bypass: correlation with their intestinal and liver content.

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.

Glucocorticoids dosing in obese subjects: A systematic review.

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.

[Opioids prescription in the vulnerable populations : the children and the elderly. Practical guidelines].

Pain management in ambulatory care regularly requires the prescription of opioids. These drugs allow adequate analgesia achievement in many patients, but inefficiency and/or intolerable side effects may limit their use. Factors related to physiological particularities, comorbidities and comedication, as well as difficulties related to drug intake and pain assessment, make children and the elderly more vulnerable to variability in opioid response and problems of safety and efficacy profile.

Phenotypic Assessment of Drug Metabolic Pathways and P-Glycoprotein in Patients Treated With Antidepressants in an Ambulatory Setting.

Objective: Drug-metabolizing enzymes (DMEs), such as cytochrome P450 (CYP) enzymes, and transporters have emerged as major determinants of variability in drug metabolism and response. This study investigated the association between CYP and P-glycoprotein activities and plasma antidepressant concentration in an outpatient clinical setting. Secondary outcomes were antidepressant efficacy and tolerance.

Effect of body weight and composition on efavirenz, atazanavir or darunavir concentration.

Background: To compare the steady state plasma concentrations (Css) of three antiretroviral drugs in both normal and overweight patients, and to determine the relationship between Css and fat mass (FM) or lean body mass.

Methods: Patients treated for more than 6 months once daily with one of the antiretroviral drugs: efavirenz (EFV) 600mg, atazanavir boosted with ritonavir (ATV-r) 300mg/100mg, or darunavir boosted with ritonavir (DRV-r) 800mg/100mg, combined with two nucleoside analogues, were enrolled prospectively. One at steady state, plasma samples for the assessment of drug concentration were taken and body composition was assessed by bioelectrical impedance.

Exploring venlafaxine pharmacokinetic variability with a phenotyping approach, a multicentric french-swiss study (MARVEL study).

Background: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders.

Binge eating behaviours in bipolar disorders.

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.

Morphine and metabolites plasma levels after administration of sustained release morphine in Roux-en-Y gastric bypass subjects versus matched control subjects.

Background: Better knowledge of opioid pharmacology after Roux-en-Y gastric bypass (RYGB) is required for optimizing their use in this growing population.

Objective: The aim of this case-controlled pharmacokinetic (PK) study was to compare morphine and its glucuronidated metabolites (morphine-3-glucuronide and morphine-6-glucuronide) plasma PKs between patients with RYGB and their controls.

Settings: University hospital, Lariboisière Hospital, Paris.

Efficacy of Venlafaxine in Neuropathic Pain: A Narrative Review of Optimized Treatment.

Purpose: The prevalence of neuropathic pain is high in the general population, and high priority is given to the management of this pain condition. The treatment of neuropathic pain remains challenging, despite the publication of national and international recommendations. The purpose of this narrative review of venlafaxine (VLX) is to provide a better knowledge of the pharmacology of this drug and a clearer view of its efficacy and tolerability in neuropathic pain.

RYGB and Drug Disposition: How to Do Better? Analysis of Pharmacokinetic Studies and Recommendations for Clinical Practice.

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.

Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort?

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.