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. 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.

Assessment of Extracorporeal Treatments in Poisoning criteria for the decision of extracorporeal toxin removal in lithium poisoning.

AIMS: To assess recommendations provided by the EXtracorporeal TReatments In Poisoning (EXTRIP) workgroup on extracorporeal toxin removal (ECTR) in lithium poisoning. METHODS: Retrospective assessment in a 128 lithium-poisoned patient cohort previously used to identify ECTR initiation criteria that could improve outcome (Paris criteria). ECTR requirement using EXTRIP criteria was compared to the actual practice or if Paris criteria were used. The potential impact on outcome if these different criteria were used was investigated. RESULTS: Using the recommended (Rec-EXTRIP) or recommended + suggested (All-EXTRIP) EXTRIP criteria, ECTR would have been indicated in more patients than was actually done (P < .001), or if Paris criteria were used (P < .01). The non-actually ECTR-treated patients fulfilling Rec-EXTRIP or All-EXTRIP criteria had shorter intensive care unit stay (P < .05) and no significant increase in fatalities and neurological impairment on discharge in comparison to the actually ECTR-treated patients. ECTR requirements using EXTRIP vs Paris criteria were not concordant (P < .001). In the non-actually ECTR-treated patients, 31/106 and 55/106 patients fulfilled Rec-EXTRIP or All-EXTRIP but not Paris criteria, respectively. Those patients had longer stay (P < .01) but no worse neurological impairment on discharge than the patients not fulfilling any of these criteria (50/106 and 26/106, respectively). In the non-actually ECTR-treated patients, 7/106 fulfilled Paris but not Rec-EXTRIP criteria. Those patients had longer stay (P < .05) and worse neurological impairment on discharge (P < .01) than the 50/106 patients not fulfilling any of these criteria. CONCLUSION: In this cohort of lithium poisonings, EXTRIP criteria may lead to more ECTR than actually performed or if the Paris criteria were used, with no demonstrated improvement in outcome.

Urinary biomarkers of exposure to glycol ethers and chlorinated solvents during pregnancy: determinants of exposure and comparison with indirect methods of exposure assessment.

OBJECTIVES: To describe urine levels of metabolites of glycol ethers and chlorinated solvents in a sample of pregnant women from the general population, to study their occupational and non-occupational determinants and to compare them with the results of indirect assessment methods of solvent exposure. METHODS: A sample of 451 pregnant women was randomly selected from a general population cohort. At inclusion, the women in this sample completed a self-administered questionnaire about their social and medical characteristics, occupation and exposure to different products at work and in non-occupational activities. Occupational exposure to solvents was assessed from the woman's self-report and from a job-exposure matrix. Eight alkoxycarboxylic acids and trichloroacetic acid and trichloroethanol were measured with chromatography in urine samples collected at inclusion. Associations between metabolite levels and job titles, exposure to products used at work, and solvent exposure were studied. RESULTS: The different glycol ether metabolites were detected in 5.3%-96.4% of the urine samples, trichloroacetic acid in 6.4% and trichloroethanol in 5.5%. Nurses had butoxyacetic acid and phenoxyacetic acid in their urine most often, whereas methoxyethoxyacetic acid was the most frequent among nursing aides. Among cleaners, ethoxyacetic acid and ethoxyethoxyacetic acid were the most frequent. The occupation of hairdresser was associated with urinary excretion of ethoxyacetic acid, ethoxyethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid. Among the women classified as exposed to solvents, the agents identified most often were ethoxyacetic acid, ethoxy-ethoxyacetic acid, butoxyacetic acid, phenoxyacetic acid, trichloroacetic acid and trichloroethanol. Ethoxyethoxyacetic acid was the only metabolite associated with non-occupational exposure. CONCLUSIONS: Metabolites of glycol ethers and chlorinated solvents were present at low levels in the urine of pregnant women. Most metabolites were associated with occupational exposure.