RÉSUMÉ
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. A therapeutic adjustment was suggested depending on the phenotyping results. From January 2017 to June 2021, we performed 32 phenotypings, 10 for adverse drug reaction, 6 for non-response, and 16 for both reasons. Depending on the CYP/P-gp evaluated, only 23% to 56% of patients had normal activity. Activity was decreased in up to 57% and increased in up to 60% of cases, depending on the CYP/P-gp evaluated. In 11/32 cases (34%), the therapeutic problem was attributable to the patient's metabolic profile. In 10/32 cases (31%), phenotyping excluded the metabolic profile as the cause of the therapeutic problem. For all ten individuals for which we had follow-up information, phenotyping allowed us to clearly state or clearly exclude the metabolic profile as a possible cause of therapeutic failure. Among them, seven showed a clinical improvement after dosage adaptation, or drug or pharmacological class switching. Our study confirmed the interest of CYP and P-gp phenotyping for therapeutic optimization in psychiatry.
RÉSUMÉ
After one year of practice, the medication reconciliation approach in follow-up and rehabilitation care was evaluated. The aim of the activity was to identify changes in treatment (CT). Three hundred and two patients benefited from the process. Some 82.2% of drug lines had voluntary TCs at discharge and all of patients had at least one TC at discharge. What are the consequences of so many TCs and what are the levers to limit these effects?
Sujet(s)
Hospitalisation , Bilan comparatif des médicaments , Sujet âgé , Continuité des soins , Études de suivi , Humains , Sortie du patientRÉSUMÉ
After one year of practice, a medication reconciliation process in geriatric aftercare was evaluated. The objective of the activity was to identify treatment changes (TC). 302 patients benefited from approach, 82.2% of changes was voluntary at hospitalization discharge and 100% of patients benefited from at least one change at hospitalization discharge. What are the consequences of so many changes and what are the measures to limit these consequences?
Sujet(s)
Hospitalisation , Bilan comparatif des médicaments , Gestion de la pharmacothérapie , Post-cure , Sujet âgé , Humains , Sortie du patientRÉSUMÉ
BACKGROUND: The combination lopinavir/ritonavir is recommended to treat HIV-infected patients at the dose regimen of 400/100â mg q12h, oral route. The usual lopinavir trough plasma concentrations are 3000-8000â ng/mL. A trend towards a 28â day mortality reduction was observed in COVID-19-infected patients treated with lopinavir/ritonavir. OBJECTIVES: To assess the plasma concentrations of lopinavir and ritonavir in patients with severe COVID-19 infection and receiving lopinavir/ritonavir. PATIENTS AND METHODS: Mechanically ventilated patients with COVID-19 infection included in the French COVID-19 cohort and treated with lopinavir/ritonavir were included. Lopinavir/ritonavir combination was administered using the usual adult HIV dose regimen (400/100â mg q12h, oral solution through a nasogastric tube). A half-dose reduction to 400/100â mg q24h was proposed if lopinavir Ctrough was >8000â ng/mL, the upper limit considered as toxic and reported in HIV-infected patients. Lopinavir and ritonavir pharmacokinetic parameters were determined after an intensive pharmacokinetic analysis. Biological markers of inflammation and liver/kidney function were monitored. RESULTS: Plasma concentrations of lopinavir and ritonavir were first assessed in eight patients treated with lopinavir/ritonavir. Median (IQR) lopinavir Ctrough reached 27â¯908â ng/mL (15â¯928-32â¯627). After the dose reduction to 400/100â mg q24h, lopinavir/ritonavir pharmacokinetic parameters were assessed in nine patients. Lopinavir Ctrough decreased to 22â¯974â ng/mL (21â¯394-32â¯735). CONCLUSIONS: In mechanically ventilated patients with severe COVID-19 infections, the oral administration of lopinavir/ritonavir elicited plasma exposure of lopinavir more than 6-fold the upper usual expected range. However, it remains difficult to safely recommend its dose reduction without compromising the benefit of the antiviral strategy, and careful pharmacokinetic and toxicity monitoring are needed.
Sujet(s)
Betacoronavirus , Infections à coronavirus/sang , Unités de soins intensifs/tendances , Lopinavir/sang , Pneumopathie virale/sang , Ventilation artificielle/tendances , Ritonavir/sang , Administration par voie orale , COVID-19 , Infections à coronavirus/traitement médicamenteux , Inhibiteurs du cytochrome P-450 CYP3A/administration et posologie , Inhibiteurs du cytochrome P-450 CYP3A/sang , Association de médicaments , Femelle , Humains , Lopinavir/administration et posologie , Mâle , Adulte d'âge moyen , Pandémies , Solutions pharmaceutiques/administration et posologie , Solutions pharmaceutiques/pharmacocinétique , Pneumopathie virale/traitement médicamenteux , Études prospectives , Ritonavir/administration et posologie , SARS-CoV-2Sujet(s)
Betacoronavirus , Infections à coronavirus/diagnostic , Infections à coronavirus/prévention et contrôle , Hydroxychloroquine/administration et posologie , Pandémies/prévention et contrôle , Pneumopathie virale/diagnostic , Pneumopathie virale/prévention et contrôle , Prophylaxie pré-exposition/méthodes , Échec thérapeutique , Sujet âgé , Antiviraux/administration et posologie , Antiviraux/sang , COVID-19 , Infections à coronavirus/sang , Association de médicaments , Humains , Hydroxychloroquine/sang , Mâle , Pneumopathie virale/sang , SARS-CoV-2RÉSUMÉ
Intranasal naloxone aims at preventing opioid overdose related deaths in active drug users. In France, it has been available since July 2016 through a temporary approval which requires a hospital-based pharmacy and a nominative registration of each patient. We present the characteristics of the first patients who could receive this prescription in our hospital-based addiction center and how they used naloxone during follow-up. Results favor a larger dispensing of naloxone. Patients' as well as peers' and families' education is needed.