Pharmacokinetics of viral antibodies after administration of intravenous immunoglobulin in patients with chronic lymphocytic leukaemia or multiple myeloma

Objective: Intravenous immunoglobulin (IVIG) preparations are derived from human pooled plasma and should fulfil high standards of purity and viral sa fety. Introduction of additional purification steps, however, may result in modulation of the biological properties of immunoglobulins. Since cleavage of the Fab-fragment leads to a significant decrease in half-life, the latt er provides information about the integrity of the immunoglobulin G (IgG) m olecules. Therefore, a pharmacokinetic study of a novel preparation is requ ired to determine safety and disposition in the target population. Methods: Twenty-seven patients with chronic lymphocytic leukaemia (CLL) and 12 with multiple myeloma received intravenous infusions of IVIG containing antibodies against hepatitis B virus (anti-HBs; n = 15; 8960 IU), cytomega lovirus (anti-CMV; n = 9; 14,250 U) or varizella-zoster-virus (anti-VZV; n = 15; 6000 IU), respectively. Serum concentrations of viral antibodies were determined for 71 days during and after infusion. Results: Maximum serum concentrations of anti-HBs, anti-CMV and anti-VZV we re observed at about 3h (median) after start of the infusion. Total body cl earances came to 0.14 +/-0.08 ml/min (anti-HBs), 0.10 +/-0.02 ml/ min (anti -CMV) and 0.14 +/-0.07 ml/min (anti-VZV). The terminal elimination half-liv es were determined to be 25.34 +/-8.34 days (anti-HBs), 24.66 +/-7.28 days (anti-CMV) and 31.79 +/- 12.47 days (anti-VZV). Clinical chemistry paramete rs including C3- and C4-complement serum concentrations revealed no patholo gical changes, seroconversion for hepatitis B and C and HIV did not occur. Conclusions: The pharmacokinetic parameters of the IgG antibodies calculate d after administration of the novel IVIG preparations to patients with CLL and multiple myeloma are in close agreement with data obtained from healthy volunteers and with values of native IgG, suggesting that the production p rocess did not impair clinically relevant characteristics of the viral impa ir clinically antibodies.