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Assessment of alteration in antiviral plasma concentration across dialysis days: computational and analytical study

Aim: Protein-bound uremic toxins (PBUTs) may displace drugs from the plasma proteins and render them more liable to clearance. This study aims to investigate the possible interplay between PBUTs and directly acting antivirals (DAAs). 

Methods: PBUT plasma protein binding was compared to those of paritaprevir (PRT), ombitasivir (OMB) and ritonavir (RTV) in silico to assess the possible competitive displacement. The three drugs were LC-MS/MS determined in seven patients across dialysis and non-dialysis days and results were compared. 

Results & conclusion: Results showed that the PBUT exhibited a lower binding than DAA reducing the liability of their competitive displacement. This was echoed by an unaltered plasma concentration across dialysis days. Results may indicate that PBUT accumulation may have limited effect on disposition of DAA.

Comments：

This study aimed to investigate the possible interaction between protein-bound uremic toxins (PBUTs) and directly acting antivirals (DAAs). In silico, the plasma protein binding of PBUT was compared to that of paritaprevir (PRT), ombitasivir (OMB), and ritonavir (RTV) to assess the possible competitive displacement. The three drugs were then determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in seven patients across dialysis and non-dialysis days, and the results were compared.

The results showed that PBUT exhibited lower binding than the DAAs, indicating a reduced liability of competitive displacement. Furthermore, the plasma concentration of the three drugs remained unaltered across dialysis days, suggesting that PBUT accumulation had limited effect on the disposition of DAAs. Therefore, the study's conclusion is that PBUT accumulation may not significantly affect the clearance of DAAs.

Overall, this study provides valuable information on the potential interaction between PBUTs and DAAs, which may have implications for the clinical use of these drugs in patients with renal impairment. However, further research is needed to confirm and expand upon these findings.

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Related Targets

HCV Protease