Célia Lloret-Linares

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

Graphical abstract Pictures displaying drug‐food (upper) drug‐herbs (lower) and drug‐dietary supplements (lower) interactions in clinical practice. Figure. No caption available. &NA; 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 Johns 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 doctors 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.

Treating mood disorders in patients with a history of intestinal surgery: a systematic review.

Bariatric surgery is increasingly being performed, with the intended benefits of significant and durable weight loss. Radical surgical resection can result in short bowel syndrome (SBS), a rare and devastating condition. Psychological distress is common in these patients. Relevant articles were identified by searching Pubmed and EMBASE databases with the following keywords: ‘Bariatrics’[Mesh] OR ‘Short Bowel Syndrome’ AND ‘Antidepressive Agents’ OR ‘Psychotropic Drugs’[Mesh]. One in-vitro study, four clinical studies and six relevant case reports were identified. Most clinical studies on antidepressant focused on the Roux-en-Y gastric bypass (RYGB); [ZERO WIDTH SPACE][ZERO WIDTH SPACE]these results are somewhat conflicting for a variety of reasons including different methodologies and small sample sizes. One month after RYGB, in patients receiving serotonin or serotonin/noradrenaline reuptake inhibitors, antidepressant levels decrease to 50% of preoperative levels and return to baseline (or greater) by 6 months in almost all patients. Other pharmacokinetic studies have shown that, 1 year after RYGB, duloxetine and sertraline levels are significantly reduced in comparison with the control population. Paradoxically, in patients with SBS and a few years after surgery, high concentration to dose ratios have been reported for citalopram and escitalopram; this may be because of an intestinal adaptation. Surgery of the intestine is likely to modify absorption and first-pass metabolism of drugs; managing the treatment of depression and anxiety in bariatric and SBS patients therefore presents a major challenge. Close clinical follow-up, associated with therapeutic drug monitoring when available, should enable the optimization of treatment response and modulate the risk of adverse events.

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

BACKGROUNDnTo 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.nnnMETHODSnPatients 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.nnnRESULTSnOne hundred and thirty-nine patients were enrolled (46, 45 and 48 in the groups EFV, ATV-r and DRV-r respectively). Their mean age was 46.2±10.4 years, 58% were male, 55.4% were from Sub Sahara African (SSA); body mass index (BMI) was 25.4±4.4kg/m2. Mean drug plasma Css of the three drugs did not differ according to BMI group. DRV-r Css tended to be higher in patients with BMI≥25kg/m2 (2896.7±1689 versus 2091.9±1038, P=0.09) and was significantly correlated with FM (r=0.3, P=0.02). In subgroup analysis, the effect of FM on DRV-r Css was significant in patients from SSA (r=0.4, P=0.04).nnnCONCLUSIONSnCss result from many factors and body composition has been shown to only weakly influence interindividual variability but should be investigated in morbidly obese patients treated with DRV-r.

Screening for genotypic and phenotypic variations in CYP450 activity in patients with therapeutic problems in a psychiatric setting, a retrospective study

Graphical abstract Figure. No caption available. Objectives: This retrospective study aimed to assess to what extent an adverse drug reaction (ADR), an abnormal therapeutic drug monitoring (TDM) or a non‐response, was attributable to an abnormal cytochrome P450 activity in a psychiatric setting. Method: We collected the results of investigations performed in these situations related to psychotropic drugs between January 2005 and November 2014. Activities of different cytochrome P450 were assessed by genotyping and/or phenotyping. Two experienced clinical pharmacologists assessed independently the possible association between the event and the results of the investigations. Results: One hundred and thirty eight clinical or biological situations had a complete assessment of all major metabolic pathways of the target drug. A majority of clinical or biological situations were observed with antidepressants (n = 93, 67.4%), followed by antipsychotics (n = 28, 20.3%), benzodiazepines and hypnotics (n = 13, 9.4%), and psychostimulants (n = 4, 2.9%). Genotype and/or phenotype determination was mainly performed because of ADRs (n = 68, 49.3%) or non‐response (n = 46, 33.3%). Inter‐rate reliability of the scoring system between the pharmacologists was excellent (kappa = 0.94). The probability of an association between ADR, TDM or non‐response and metabolic status was rated as intermediate to high in 34.7% of all cases, with proportions of 30.4% and 36.7%, for non‐response and ADR respectively. Conclusion: When indicated by clinical pharmacologists, ADR, TDM or non‐response may be attributable to a variation of the metabolic status with an intermediate to high probability in 34.7% of patients, based on the congruent assessment made by two clinical pharmacologists. Further studies assessing the clinical relevance of prospective explorations and clarifying the appropriate method according to the clinical context are needed.