Objective: Intravenous immunoglobulin (IVIG) preparations are derived from human pooled plasma and should fulfil high standards of purity and viral safety. 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 latter provides information about the integrity of the immunoglobulin G (IgG) molecules. Therefore, a pharmacokinetic study of a novel preparation is required 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), cytomegalovirus (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 were observed at about 4 h (median) after start of the infusion. Total body clearances 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-lives 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 parameters including C3- and C4-complement serum concentrations revealed no pathological changes, seroconversion for hepatitis B and C and HIV did not occur.
Conclusions: The pharmacokinetic parameters of the IgG antibodies calculated 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 process did not impair clinically relevant characteristics of the viral antibodies.