Prospective Analysis of Factors Influencing Inter-Individual Variation in Trough Plasma Voriconazole Concentrations in Older Patients-Impact of High α1-Acid Glycoprotein Levels.
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引用次数: 0
Abstract
Voriconazole (VRCZ), an azole-based, deep-seated antifungal agent, is used as a 1st-line treatment for aspergillosis in Japan. VRCZ exhibits nonlinear pharmacokinetic (PK) behavior with relatively large inter-individual variability in plasma concentration. Additionally, genetic polymorphisms of CYP2C19 have been reported to influence the metabolic variability of VRCZ. The purpose of this study was to search for and identify clinically relevant potential factors influencing the PK and plasma concentration of VRCZ to better inform VRCZ dosing regimens. Thirty patients receiving VRCZ were enrolled. Total (Ct) and unbound (Cu) trough plasma concentrations of VRCZ were determined by the HPLC-UV method. Univariate and multivariate correlation analyses were used to evaluate the relationships between Ct or Ct/dose per body weight (Ct/D) and individual demographic and laboratory characteristics. Since the increasing trend of C-reactive protein (CRP) inversely correlated with the classification of CYP2C19 gene polymorphisms, it was suggested that the inflammation counteracted the trend of Ct according to CYP2C19 gene polymorphisms. Spearman's rank-order correlation analysis showed significant correlations between Ct and dose per body weight, CRP, and α1-acid glycoprotein (α1-AGP). Multivariate linear regression analysis showed that age, dose per body weight, CRP, and α1-AGP were significant explanatory factors for Ct. In particular, elevated α1-AGP levels were found to have significant explanatory value for decreased Ct. Although the present study has critical limitations, such as the patient sample was small in size and being limited to a single medical institution, this finding may explain some of the inter-individual variability in plasma VRCZ concentration.
期刊介绍:
Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012.
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