4 research outputs found
āļāļēāļĢāļēāļĄāļīāđāļāļāļĢāđāļāļēāļāđāļ āļŠāļąāļāļāļĨāļāļĻāļēāļŠāļāļĢāđāļāļāļāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāđāļāđāļāļāļēāļĄāļāļĩāđāļāđāļāļāđāļāļāļ CYP2C19 Voriconazole Pharmacokinetic Parameters Based on CYP2C19 Phenotype
āļāļāļāļąāļāļĒāđāļ āļ§āļąāļāļāļļāļāļĢāļ°āļŠāļāļāđ: āđāļāļ·āđāļāļŦāļēāļāđāļēāļāļēāļĢāļēāļĄāļīāđāļāļāļĢāđāļāļēāļāđāļ āļŠāļąāļāļāļĨāļāļĻāļēāļŠāļāļĢāđāļāļāļāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāļāļķāđāļāļāļ°āļāļģāđāļāļŠāļđāđāļāļāļēāļāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāļāļĩāđāđāļŦāļĄāļēāļ°āļŠāļĄāđāļāļĒāđāļāđāļāļāļēāļĄāļāļĩāđāļāđāļāļāđāļāļāļ CYP2C19 āđāļāļ·āđāļāđāļŦāđāđāļāđāļĢāļ°āļāļąāļāļĒāļēāļāđāļģāļŠāļļāļāđāļāđāļĨāļ·āļāļāļāļĒāļđāđāđāļāļāđāļ§āļāļāļēāļĢāļĢāļąāļāļĐāļēāļāļĩāđ 1-5 āļĄāļ./āļĨāļīāļāļĢ āļ§āļīāļāļĩāļāļēāļĢāļĻāļķāļāļĐāļē: āļāļēāļĢāļ§āļīāļāļąāļĒāđāļāļīāļāļŠāļģāļĢāļ§āļāđāļāļĒāļāļēāļĢāđāļāđāļāļāđāļāļĄāļđāļĨāļĒāđāļāļāļŦāļĨāļąāļāļāļēāļāđāļ§āļāļĢāļ°āđāļāļĩāļĒāļāļāļāļāļāļđāđāļāļ§āļĒāļāļđāđāđāļŦāļāđāļāļĩāđāđāļāđāļĢāļąāļāļāļēāļĢāļĢāļąāļāļĐāļēāļāđāļ§āļĒāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāļĢāļ°āļŦāļ§āđāļēāļāđāļāļ·āļāļāļĄāļāļĢāļēāļāļĄ 2555 āļāļķāļāļĄāļĩāļāļēāļāļĄ 2559 āļ āđāļĢāļāļāļĒāļēāļāļēāļĨāļĢāļēāļĄāļēāļāļīāļāļāļĩ āļāđāļāļĄāļđāļĨāļāļąāļāļāļĨāđāļēāļ§ āđāļāđāđāļāđ āļāļēāļĒāļļ āđāļāļĻ āļāđāļģāļŦāļāļąāļ āļāļĩāđāļāđāļāļāđāđāļĨāļ°āļāļĩāđāļāđāļāļāđāļāļāļ CYP2C19 āđāļāļāđāļāļāļāļēāļĢāđāļŦāđāļĒāļēāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāđāļĨāļ°āļĢāļ°āļāļąāļāļĒāļēāļāđāļģāļŠāļļāļāđāļāđāļĨāļ·āļāļ āđāļĨāđāļ§āļāļģāļāļ§āļāļāđāļēāļāļēāļĢāļēāļĄāļīāđāļāļāļĢāđāļāļēāļāđāļ āļŠāļąāļāļāļĨāļāļĻāļēāļŠāļāļĢāđāļāļāļāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāđāļāļĒāđāļāđāļŠāļĄāļāļēāļĢ Michaelis-Menten āļāļēāļāļāļąāđāļāļāļģāļāļ§āļāļāļāļēāļāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāđāļāļ·āđāļāđāļŦāđāļĢāļ°āļāļąāļāļĒāļēāļāļĒāļđāđāđāļāļāđāļ§āļāļāļēāļĢāļĢāļąāļāļĐāļēāđāļāđāļāļāļēāļĄāļāļĩāđāļāđāļāļāđāļāļāļ 2C19 āļāļĨāļāļēāļĢāļĻāļķāļāļĐāļē:āļāļēāļāļāļđāđāļāđāļ§āļĒāļāļąāđāļāļŦāļĄāļ 53 āļĢāļēāļĒ āđāļāđāļāđāļāļĻāļāļēāļĒ 29 āļĢāļēāļĒ (54.7%) āļāļēāļĒāļļāđāļĨāļ°āļāđāļģāļŦāļāļąāļāđāļāļĨāļĩāđāļĒ 52.98 āļāļĩ āđāļĨāļ° 57.97 āļāļīāđāļĨāļāļĢāļąāļĄ āļāļēāļĄāļĨāļģāļāļąāļ āļāđāļēāļĄāļąāļāļĒāļāļēāļāļāļāļāļāđāļēāļāļāļāļĩāđ Michaelis-Menten (Km) āļŠāļģāļŦāļĢāļąāļāļāļđāđāļāļĩāđāļĄāļĩāļāļĩāđāļāđāļāļāđāļāļāļ CYP2C19 āđāļāļ extensive metabolizer (EM) āđāļĨāļ° āđāļāļ non-extensive metabolizer (non-EM) āđāļāđāļēāļāļąāļ 0.262 āļĄāļ./āļĨāļīāļāļĢ āđāļĨāļ° 0.666 āļĄāļ./āļĨāļīāļāļĢ āļāļēāļĄāļĨāļģāļāļąāļ (P-value = 0.008) āļāđāļēāļĄāļąāļāļĒāļāļēāļāļāļāļāļāļąāļāļĢāļēāļāļēāļĢāđāļĄāļāļēāļāļāļĨāļīāļŠāļĄāļĒāļēāļŠāļđāļāļŠāļļāļ (Vmax) āļŠāļģāļŦāļĢāļąāļ EM āđāļĨāļ° non-EM āđāļāđāļēāļāļąāļ 0.425 āļĄāļ./āļāļ./āļāļĄ. āđāļĨāļ° 0.483 āļĄāļ./āļāļ./āļāļĄ. āļāļēāļĄāļĨāļģāļāļąāļ (P-value = 0.262) āļāļāļēāļāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāļāļĩāđāđāļāļ°āļāļģāđāļāļ·āđāļāđāļŦāđāđāļāđāļĢāļ°āļāļąāļāļĒāļēāļāđāļģāļŠāļļāļāđāļāđāļĨāļ·āļāļāļāļĒāļđāđāđāļāļāđāļ§āļ 1 - 5 āļĄāļ./āļĨāļīāļāļĢ āđāļāđāļēāļāļąāļ 8.9 - 10.7 āļĄāļ./āļāļ./āļ§āļąāļ āđāļĨāļ° 6.7 - 9.9 āļĄāļ./āļāļ./āļ§āļąāļ āļŠāļģāļŦāļĢāļąāļ EM āđāļĨāļ° non-EM āļāļēāļĄāļĨāļģāļāļąāļ āđāļĨāļ°āđāļāļ·āđāļāđāļŦāđāļŠāļ°āļāļ§āļāđāļāļāļēāļāļāļāļīāļāļąāļāļī āļāļāļēāļāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāļāļĩāđāđāļāļ°āļāļģāļŠāļģāļŦāļĢāļąāļ EM āđāļĨāļ° non-EM āđāļāđāļēāļāļąāļ 10 āļĄāļ./āļāļ./āļ§āļąāļ āđāļĨāļ° 8.5 āļĄāļ./āļāļ./āļ§āļąāļ āļāļēāļĄāļĨāļģāļāļąāļ āđāļāļ·āđāļāđāļŦāđāđāļāđāļĢāļ°āļāļąāļāļĒāļēāļāđāļģāļŠāļļāļāđāļāđāļĨāļ·āļāļāļāļĢāļ°āļĄāļēāļ 2 āļĄāļ./āļĨāļīāļāļĢ āļŠāļĢāļļāļ: āļāļēāļĢāļĻāļķāļāļĐāļēāļāļĩāđāđāļŦāđāļāđāļāļĄāļđāļĨ Km,Vmax āđāļĨāļ°āļāļāļēāļāļĒāļēāļ§āļāļĢāļīāđāļāļāļēāđāļāļĨāļŠāļģāļŦāļĢāļąāļāļāļđāđāļāđāļ§āļĒāļāļđāđāđāļŦāļāđāđāļāļĒāđāļāđāļāļāļēāļĄāļāļĩāđāļāđāļāļāđāļāļāļ CYP2C19 āđāļāđāļāļēāļāļāđāļē Km āđāļĨāļ° Vmax āļāļĩāđāļĄāļĩāļāļ§āļēāļĄāđāļāļĢāļāļĢāļ§āļāļāđāļāļāļāđāļēāļāļĄāļēāļāļāļīāļāļēāļĢāļāļēāļāļēāļāļāđāļ§āļāļāļĩāđāļāļ§āđāļēāļ āļāļķāļāļĒāļąāļāđāļĄāđāđāļāļ°āļāļģāđāļŦāđāđāļāđāļāļāļēāļāļĒāļēāļāļĩāđāļāļģāļāļ§āļāđāļāđāļāļēāļāļāļēāļĢāļĻāļķāļāļĐāļēāļāļĩāđāļāļāļāļ§āđāļēāļāļ°āđāļāđāļāļāļŠāļāļāļāļ§āļēāļĄāđāļŦāļĄāļēāļ°āļŠāļĄāļāļāļāļāļāļēāļāļĒāļēāļāļąāļāļāļĨāđāļēāļ§ āļāļēāļĢāļāļīāļāļāļēāļĄāļāļĢāļ§āļāļ§āļąāļāļĢāļ°āļāļąāļāļĒāļēāđāļāđāļĨāļ·āļāļāļāļķāļāļĒāļąāļāļāļģāđāļāđāļ āļāļģāļŠāļģāļāļąāļ: āļ§āļāļĢāļīāđāļāļāļēāđāļāļĨ, āļāļĩāđāļāđāļāļāđāļāļāļ CYP2C19, āđāļ āļŠāļąāļāļāļĨāļāļĻāļēāļŠāļāļĢāđāđāļāļāđāļĄāđāđāļāđāļāđāļŠāđāļāļāļĢāļ, āļāļāļēāļāļĒāļēāđāļāļ°āļāļģÂ AbstractObjective: To determine pharmacokinetic parameters of voriconazole (VRZ) that will lead to finding appropriate VRZ dose to maintain trough concentration (Ctr) within target therapeutic range of 1-5 mg/L based on CYP2C19 phenotype. Methods: The medical records of adult patients who received VRZ treatment between January 2012 and March 2016 at Ramathibodi Hospital were retrospectively reviewed. Patientâs data including gender, age, body weight, CYP2C19 genotype and phenotype, VRZ dosing regimen, and VRZ Ctr were collected. The pharmacokinetic parameters of VRZ were calculated using conventional nonlinear pharmacokinetic study, i.e., Michaelis-Menten equation. Proper dose for keeping VRZ Ctr within therapeutic range were then determined for each CYP2C19 phenotype. Results: A total of 53 patients were included into this study. Twenty-nine (54.7%) were male with mean age and body weight of 52.98 yrs and 57.97 kg, respectively. Median Michaelis-Menten constant (Km) for CYP2C19 extensive metabolizers (EM) and non-extensive metabolizers (non-EM) were 0.262 mg/L and 0.666 mg/L, respectively (P-value = 0.008). Median maximum rate of metabolism (Vmax) for EM and non-EM were 0.425 mg/kg/h and 0.483 mg/kg/h, respectively (P-value = 0.262). The doses to achieve therapeutic Ctr (1 - 5 mg/L) were 8.9 - 10.7 mg/kg/day and 6.7 - 9.9 mg/kg/day for EM and non-EM, respectively. For more applicable in real world practice, the rounded dose of 10 mg/kg/day and 8.5 mg/kg/day for EM and non-EM, respectively, were recommended to provide VRZ Ctr around 2 mg/L. Conclusion: This present study provided Michaelis-Menten constant (Km and Vmax) of VRZ for Thai adult patients and the dose recommendation for this patient group based on CYP2C19 phenotype. The Km and Vmax of VRZ in this study show high variability judged from their wide range, therefore our recommended doses still cannot be used in practice unless its appropriate would be validated. Therapeutic drug monitoring of VRZ is still warranted. Keywords: voriconazole, CYP2C19 phenotype, nonlinear pharmacokinetic, dose recommendation
A case of naganishial pleuritis in a kidney transplant recipient
Abstract The Naganishia species is a mycosis, previously classified as a nonâneoformans Cryptococcus species. The increased number of naganishial infections occurs predominantly in immunocompromised conditions, especially in people living with HIV with low CD4 cell count, primary immunodeficiencies, and iatrogenic immunosuppression. The lungs can serve as the primary site of infection, leading to various pulmonary manifestations. However, naganishial pleural effusions are unrecognized and challenged in diagnosis because of their presentation, which can mimic tuberculous pleural effusion. Herein, we report the case of a 53âyearâold man who had undergone kidney transplantation for more than 2âyears and presented with chest tightness and dyspnea. Computed chest tomography demonstrated left pleural nodules and pleural effusion, later confirmed as exudative pleural effusion with a lymphocyte predominance. Pleuroscopy revealed multiple small pleural nodules, and biopsies of these nodules were performed. Naganishia spp. was identified by the 18S rRNA sequencing technique
Author Correction: Longitudinal study of disease severity and external factors in cognitive failure after COVID-19 among Indonesian population
Longitudinal study of disease severity and external factors in cognitive failure after COVID-19 among Indonesian population
Abstract The COVID-19 infection is assumed to induce cognitive failure. Identifying the relationship between COVID-19, the effect of vaccination and medication, and accommodating non-COVID-19 factors to cognitive failure is essential. This study was conducted in Indonesia from September 2021 to January 2023. Demographic information, clinical data, comorbidities, vaccination, and medication during COVID-19 were obtained, as well as a 6-month cognitive assessment with Cognitive Failures Questionnaire/CFQ, Fatigue Severity Score, and Generalized Anxiety Disorder (GAD-7). A Structural Equation Model explains the relationship between potential predictors and cognitive failure. The average score of CFQ after 6 months was 45.6âÂąâ23.1 out of 100. The severity of the disease, which was associated with vaccination status, age, previous infection, and unit of treatment (pââ0.05). This study concludes that cognitive failure after COVID-19 is a multifactorial event and does not solely depend on COVID-19 severity. It is crucial to re-address the factors related to the long-term efficacy of vaccination and medication and focus on non-health factors affecting cognitive failure. Trial Registration: NCT05060562