Variation Study of Steady-State trough Concentration of Adalimumab in Serum of Patients with Ankylosing Spondylitis / 中国药学杂志

ABSTRACT

OBJECTIVE: To establish an enzyme-linked immunosorbent assay (ELISA) method for determining the concentration of adalimumab in human serum to determine the steady-state trough concentration of adalimumab in patients with ankylosing spondylitis (AS) and to study inter- and intraindividual variation. METHODS: Human tumor necrosis factor α (hTNF-α) was coated on the solid phase microplate as the capture antigen, and the sample to be tested was added. The goat anti-human IgG-HRP was used as the detection antibody and TMB was used for color development. The absorbance at 450 nm was finally determined. Forty-seven patients with AS treated with standard dose of adalimumab injection were included. Blood samples of steady-state after 12 to 24 weeks′ treatment were collected to determine trough drug concentrations. RESULTS: The quantitative range of the method was 0.63-20.00 μg•mL-1. The inter-assay and intra-assay precisions were not more than 15% and the average recovery was <110%. The median serum concentration of 47 patients was 10.15 μg•mL-1 (IQR4.36~13.31 μg•mL-1) and ranged from 0.00-23.71 μg•mL-1 with an inter-individual variation of 63%; the median variation of intra-individuals within 43 patients was 11% (IQR 8%-17%). CONCLUSION: This method is stable and is suitable for the detection of clinical samples. Pronounced inter- but not intraindividual variation was observed in adalimumab trough levels in steady state. The "reaction therapeutic drug monitoring" based on the steady-state trough concentration will facilitate the adjustment of the dosing regimen.