Читать книгу Recent Advances in the Pathogenesis and Treatment of Kidney Diseases - Группа авторов - Страница 23

Rituximab is composed of 2 heavy chains of 451 amino acids and 2 light chains of 213 amino acids, with a molecular weight of 145 kD. Rituximab has a binding affinity for the CD20 antigen of approximately 8.0 nM. The mean serum half-life of rituximab was reported to be 10–15 days in patients with steroid-dependent nephrotic syndrome [7]. In a single-dose study in subjects with renal failure, the substantial half-life was found to range from 10 to 14 days [8]. In a small, single-dose, dose-escalation study, 50 mg/m² resulted in the same degree and duration of peripheral B-cell suppression and the same effect on the antibody response as 375 mg/m²[9].

In human disease states for which rituximab is administered, circulating B cells are rapidly eliminated. Some preliminary data suggest that a single dose of rituximab can deplete tissue CD20-positive cells in transplant recipients [10]. B-cell recovery begins at approximately 6 months following the completion of treatment [11]. The median B-cell levels return to normal by 12 months after the completion of treatment. Even once the total B-cell count returns to normal, a change in phenotype appears to occur, with the B cells present being relatively deficient in the expression of CD27, a surface marker of memory B cells [12]. This finding suggests that the B cells that do repopulate are primarily naïve, at least as late as 2 years after a single dose.