Plasma protein binding of arsenic species in acute promyelocytic leukemia patients and their relationships with hepatic and renal function.

Abstract

Objectives: Percentage protein binding (%PB) of arsenic species in acute promyelocytic leukemia (APL) patients treated with arsenic trioxide remains unclear. It can be different depending on the status of hepatic or renal function.

Methods: This study obtained steady-state blood samples from normal APL patients and those with hepatic or renal impairment. %PB of inorganic arsenic (iAs), monomethylarsonic acid (MMA^V), and dimethylarsinic acid (DMA^V) was determined by analyzing free and total plasma concentrations using ultrafiltration method by HPLC-HG-AFS.

Results: There is a linear relationship between free and total plasma concentrations for iAs (r² = 0.952), MMA^V (r² = 0.603), and DMA^V (r² = 0.945). For patients with normal hepatic and renal function, mean %PB was as follows: iAs at 26.7 ± 14.3%, MMA^V at 53.3 ± 11.9%, and DMA^V at 24.7 ± 7.8%. %PB decreased in patients with renal impairment, with MMA^V and DMA^V showing statistically significant differences (p < 0.05 for MMA^V, p < 0.01 for DMA^V). No significant differences in %PB between normal and hepatic impairment group were observed.

Conclusion: Free arsenic species fraction can be estimated by total concentration. DMA^V and iAs present low %PB, while MMA^V exhibits a relatively high %PB in plasma. Level of %PB is more likely to be affected by renal function and age.