When is protein binding important

Abnormal liver function occurred in 5 patients 2. Rash occurred in 3 patients 1. Abnormal audition occurred in 3 patients 1. However, there was still wide inter-individual variability in plasma concentration of VRC mostly associated with the diversity of metabolic types CYP2C19 Hamadeh et al.

Unbound concentration of 79 plasma samples were separated by RED, and showed a positive relationship with C t , which was consistent with the result from Florent et al. Florent et al. From the result of our in vitro studies, C u was also influenced by C t and the protein concentration.

Samples with a lower protein concentration or a higher C t were associated with a significantly higher C u. It was influenced by some other factors, such as the CYP2C19 metabolic types, liver function of patients, and co-administration during the treatment. The similar relationship appeared in minimum C t , but the p value in C u was lower which indicated that C u may be more sensitive to the metabolic type of CYP2C19 than C t.

Data analysis showed that the maximum C t and C u were both in a higher level when AST was in an abnormal situation. However, there was no similar result occurred in ALT values in our research. This might have been due to the co-administration with hepatoprotectants glutathione, polyene phosphatidylcholine. ALT is mainly distributed in hepatocytes, so the variation of ALT may be influenced when used hepatoprotectants in combination.

AST is mainly distributed in the cardiac, which may be influenced less by the liver function. These are different from the results reported from Vanstraelen et al. Subjects in this study were patients with malignant blood diseases. There were many concomitant medications during the treatment of malignant blood diseases. C u of voriconazole may also be affected by these combinations. These results indicated that the concomitant medication may be a factor that influence the plasma concentration of VRC.

The C u in patients co-administered with or without lansoprazole should be analyzed if there was enough cases. C u was influenced by a lot of factors. In our study, the relationship between C u and ADRs was analyzed for the first time. The unbound C max in patients with ADRs reversible visual changes; neurological abnormity or mental abnormity, such as nightly excitement, lack of alertness, and unconsciousness were significantly higher than those without ADRs, while there was no similar result in C t , which indicated that C u showed a more sensitive relationship with ADRs than C t.

The protein binding characteristics of VRC was also investigated in our study. The PPB was significantly higher in patients than all the in vitro samples, which was consistent with Florent et al. PPB was higher in sample with higher C t or higher protein concentration. This positive relationship occurred both in patient plasma samples and in in-vitro samples, and was more obvious in AAG samples.

This is not consistent with previous study Vanstraelen et al. It may be caused by the different device used for equilibrium dialysis. Thus, the relationship between total PPB and PPB of individual protein is not a simple addition, but a compressive combination.

In this study, equilibrium dialysis ED , the most common methods was used for investigating drug protein binding characteristics. ED is typically considered to be the gold standard Zhang et al. More cases should be taken into analysis in the future study. VRC plasma protein binding rate in patient was significantly higher The relationship between unbound drug concentration and ADRs is more sensitive than that total plasma concentration do.

The datasets generated for this study are available on request to the corresponding authors. The studies involving human participants were reviewed and approved by the Ethical Committee of Jiangsu Province Hospital. QC and LY performed the genetic analyze. Z-Q-YY performed the statistical analyses. All authors were involved in drafting or reviewing the manuscript and approved the final version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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