This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of… Click to show full abstract
This prospective observational study aimed to clinically describe voriconazole administrations and trough concentrations in patients with Child–Pugh class C and to investigate the variability of trough concentration. A total of 144 voriconazole trough concentrations from 43 Child–Pugh class C patients were analyzed. The majority of patients (62.8%) received adjustments. The repeated measured trough concentration was higher than the first and final ones generally (median, 4.33 vs. 2.99, 3.90 mg/L). Eight patients with ideal initial concentrations later got supratherapeutic with no adjusted daily dose, implying accumulation. There was a significant difference in concentrations among the six groups by daily dose (p = 0.006). The bivariate correlation analysis showed that sex, CYP2C19 genotyping, daily dose, prothrombin time activity, international normalized ratio, platelet, and Model for end-stage liver disease score were significant factors for concentration. Subsequently, the first four factors mentioned above entered into a stepwise multiple linear regression model (variance inflation factor <5), implying that CYP2C19 testing makes sense for precision medicine of Child–Pugh class C cirrhosis patients. The equation fits well and explains the 34.8% variety of concentrations (R2 = 0.348). In conclusion, it needs more cautious administration clinically due to no recommendation for Child–Pugh class C patients in the medication label. The adjustment of the administration regimen should be mainly based on the results of repeated therapeutic drug monitoring.
               
Click one of the above tabs to view related content.