Population Pharmacokinetics of Voriconazole in Chinese Patients with Hematopoietic Stem Cell Transplantation
Adult
Male
0301 basic medicine
Antifungal Agents
Genotype
Hematopoietic Stem Cell Transplantation
Biological Availability
Middle Aged
Models, Biological
3. Good health
Cytochrome P-450 CYP2C19
Young Adult
03 medical and health sciences
Asian People
Nonlinear Dynamics
Humans
Female
Voriconazole
Drug Monitoring
Aged
Retrospective Studies
DOI:
10.1007/s13318-019-00556-w
Publication Date:
2019-04-30T18:47:51Z
AUTHORS (8)
ABSTRACT
Voriconazole is widely recommended for the prevention and treatment of invasive fungal infections in hematopoietic stem cell transplantation patients. However, its use is limited by a narrow therapeutic range and large inter-individual variability. This study aimed to characterize the pharmacokinetics of voriconazole in Chinese hematopoietic stem cell transplantation patients, to explore factors affecting its pharmacokinetic parameters, and to provide recommendations for its optimal dosing regimens.A total of 121 serum concentration samples from 23 patients were retrospectively included. Voriconazole concentrations were detected, and patient clinical data were recorded. Population pharmacokinetic analysis was performed by a non-linear, mixed-effect modeling approach. Goodness-of-fit plots, bootstrap method, prediction-corrected visual predictive check and external validation by an independent group of seven patients were performed to evaluate the final model.A one-compartment model with first-order elimination successfully described the data. The absorption rate constant was fixed at 1.1 h-1 and bioavailability was fixed at 0.895. The typical values for voriconazole clearance and distribution volume were 9.52 L/h and 155 L, respectively. CYP2C19*2 genotype and mycophenolate mofetil combination presented a significant impact on the clearance. Compared with CYP2C19*2 carriers, voriconazole clearance was proven to be higher in CYP2C19*1/*1 patients.A population pharmacokinetic model of voriconazole was successfully established in Chinese hematopoietic stem cell transplantation patients. Based on the final model, CYP2C19*2 genotyping coupled with therapeutic drug monitoring seems to be useful to guide voriconazole dosing and to explain subtherapeutic concentrations in clinical practice.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (32)
CITATIONS (13)
EXTERNAL LINKS
PlumX Metrics
RECOMMENDATIONS
FAIR ASSESSMENT
Coming soon ....
JUPYTER LAB
Coming soon ....