View clinical trials related to Voriconazole.
Filter by:Invasive fungal infections are a significant cause of morbidity and mortality in immunocompromised host such as prolong neutropenic patients , post transplantation patients, malignancies or advanced AIDS . The majority of these infections were caused by Aspergillus species, which the first line of treatment is antifungal agent, Voriconazole , a triazole antifungal drug which was approved by the Food and Drug Administration in May 2002 for the treatment of invasive aspergillosis and refractory infections of Scedosporium apiospermum and Fusarium spp. There are two forms of Voriconazole , oral and intravenous form. The recommendation dose is 6 mg/kg twice daily for two dosages, followed by 4 mg/kg twice daily in intravenous form or a loading dose of 400 mg twice daily for two doses is used (for individuals >40 kg), followed by 200 mg twice daily, and in individuals <40 kg the maintenance dose is 100 mg twice daily in oral form. Voriconazole has a narrow therapeutic window and nonlinear pharmacokinetic profile with wide inter-individual and intra-individual variability, such as age, race, genotypic variation, liver dysfunction, the presence of food and drug-drug interactions with CYP450 inhibitors. These large variations in pharmacokinetics may be associated with decreased efficacy or increased toxicity. Therefore , monitoring of serum trough concentrations is recommended in the following infections: invasive aspergillosis treatment , endophthalmitis; meningitis or osteoarticular infections due to Exserohilum rostratum. In Thai population , there are different genetic polymorphism from Caucasian ,resulting in a different response to the initial dose and there is limited resources in Thailand , mostly patients are unaccessible for Voriconazole level. Especially,in the period of starting drug, which is the critical period for patients ,most of them are post chemotherapy which may have gastrointestinal problems, mucositis , vomiting or diarrhea ,as well as receiving multiple concurrent medications. All of these affect drug absorption,drug level and efficacy of treatment. Thus, this study was designed to evaluated Voriconazole level in Thai patients in the first two week after administration. Primary question - From the first collected of Voriconazole drug level , Are the invasive fungal infection patients in King Chulalongkorn Memorial Hospital achieved the drug level more than 60% ? Secondary question - Which factor affecting Voriconazole through level in the first two weeks after administration? Research Design - Observational Studies (Descriptive retrospective and prospective study) Research Methodology Target Population - Patients received Voriconazole for treatment or prophylaxis invasive fungal infection Study population - Patients in King Chulalongkorn Memorial hospital received Voriconazole for treatment or prophylaxis invasive fungal infection Sample size n= ZZ/2P(1-P) /dd - n = sample size - P =Incident rate - From the pilot study of 15 Invasive fungal infection patients in King Chulalongkorn memorial hospital from February to September 2015 , 60% ( 9 of 15 patients) of the first collected of Voriconazole trough level achieved the therapeutic level. replaced P = 0.6 - Z = 95% confident interval = 1.96 - d = acceptable error = 0.10 n = (1.96) (1.96) (0.60)(1-0.60) / (0.10)(0.10) n =92 , sample size = 92 Study processing and data collection Data collection - Collected data of patients received Voriconazole in first two weeks of treatment or prophylaxis invasive fungal infection in King Chulalongkorn Memorial hospital in 2015-2017 from outpatient records , inpatient records and computer database in King Chulalongkorn Memorial hospital. This data included - Baseline characteristics : sex, age ,weight ,BMI ,co-morbid ,personal history of smoking or alcohol drinking - Basic laboratory investigation : complete blood count , Creatinin , liver function test , albumin level - Gastrointestinal problems - Indication of Voriconazole treatment - Data of invasive fungal infection : - Data of Voriconazole usage : Loading dose, Maintenance dose, Trough level , Data of drug adjustment, Concurrent medication used, Side effect - All data was summarized and recorded in case report forms. Data Analysis and Statistics The data was analysed by computer using SPSS17 program This study used descriptive statistics ,describing general information, age, results, laboratory results and side effects of the drug in mean ,percentage or standard deviation. And used the chi-square test for analysis of the proportion of patients with serum drug levels within the therapeutic range. This study used a confidence level of 95%, p-value less than 0.05 was statistically significant.
Hypothesis: A pharmacogenetic score integrating both CYP3A genotypes could be influence initial trough voriconazole plasma concentrations and thus useful to adapt a priori voriconazole dosing in order to get adequate voriconazole exposure as possible after starting treatment. Main Objective: To determine predictive value of a combined pharmacogenetic score on onset of trough voriconazole plasma concentration inferior than lower therapeutic target.
The objective of this study is to obtain the absolute bioavailability of voriconazole in critically ill ICU patients, because pharmacokinetics can be different in critically ill patients due to alterations in function of various organs and body systems compared with healthy volunteers.
The death rate in children from the invasive fungal infection called aspergillosis is more than 50%. Voriconazole is the first-line therapy for this infection. In a previous publication the investigators have shown a highly significant relationship between voriconazole plasma concentrations and survival. However, voriconazole dosing is currently poorly established, and plasma drug exposure varies between children by 400% or more, even after intravenous dosing. The objective of this study is to investigate the reasons for this variability in voriconazole pharmacokinetics (PK).In two studies, the investigators will enroll 80 children/adolescents receiving oral or intravenous voriconazole, divided by age under 2 years (n=15), and 2-18 years (n=65). From each patient the investigators will collect the following: 1) a blood sample for detection of several genetic changes known to affect drug metabolizing enzyme (DME) activity; 2) up to 9 blood samples after a voriconazole dose for measurement of voriconazole ("PK sampling"); 3) follow-up samples after each PK sampling visit if necessary to adjust the dose so that voriconazole concentrations in the blood are satisfactory (known as therapeutic drug monitoring or TDM). At the time of the voriconazole dose prior to the PK sampling, we will also give single IV or oral (corresponding to the route of voriconazole administration) low doses of esomeprazole (an antacid), midazolam (a sedative), and ranitidine (an antacid) as a cocktail to test or probe DME activity. All of these medications are used commonly in children already. The investigators will estimate DME activity or phenotype using ratios of probe drug metabolite to parent drug concentrations, while simultaneously quantifying the amount of DME genetic material (mRNA) and protein in white blood cells. The investigators will test associations between DME activity, mRNA, protein, voriconazole PK, age, sex, and degree of illness. The investigators will also use a computer program to integrate all these data to develop a comprehensive model that will predict blood concentrations of voriconazole in children of all ages, as well as assist physicians and pharmacists to dose voriconazole more accurately.The total study duration for each subject will be until after the TDM follow up visit, generally about one week.
The Pharm A project is a French national collaborative project aiming to determine the population pharmacokinetics of ceftazidime, ciprofloxacin, and voriconazole in paediatric patients aged one month to five years.