In two independent trials 10 and 12 healthy volunteers received the novel intravenous immunoglobulin (IVIG) preparations BT 511 and BT 507, respectively. BT 511 contains 5 g human plasma proteins per 100 ml, more than 95% of which are immunoglobulins of the G class (IgG). BT 507 contains in addition 61 IU antibody against hepatitis B surface antigen (anti-HBs).ml-1. In trial I volunteers received 4.0 ml/kg (n = 4) and 8.0 ml.kg-1 (n = 6) BT 511 to study the tolerability and the magnitude of the increase in immunoglobulins in plasma as well as their decline over 1 month. After administration of the lower dose, plasma IgG increased from 10.7 to 14.7 g.l-1 directly after the infusion. Following the 8.0 ml.kg-1 dose a more pronounced increase from 12.4 to 21.2 g.l-1 was observed. No adverse events occurred. After 1 month IgG concentrations had almost reached baseline values at 12.2 g.l-1 in the 4.0 ml.kg-1 group, but were still significantly increased at 15.2 g.l-1 after the high dose. There was a linear correlation between the maximal IgG plasma concentration and the subsequent decline of IgG during the 29-day observation period. After administration of BT 507 maximal anti-HBs concentrations of 1778 mU.ml-1 occurred 1.4 h after termination of the infusion. The terminal elimination half-life was 22.4 days, and total clearance and volume of distribution were determined to be 0.122 ml.min-1 and 5.41, respectively. The pharmacokinetic parameters calculated for anti-HBs as an indicator of IgG were in accordance with the pharmacokinetic behaviour of native IgG.

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.

Adverse drug reactions (ADR) occur in about 5% of all pharmacologically treated patients. Between 2% and 20% of all hospital admissions are caused by ADR, and approximately 10% of all hospitalized patients experience ADR during their hospital stay. Several thousand patients die due to ADR in Germany each year. ADR-associated drugs come predominantly from the class of non-steroidal antiinflammatory drugs, anticoagulants, acetylsalicylic acid and cardiovascular drugs. Most ADR cases present as gastrointestinal bleeding and adverse cardiovascular effects. Apart from this, one or more drugs are withdrawn from the market each year because of unwanted but mostly rare side effects. In recent years the most prominent cases were rofecoxib, cisapride and cerivastatin. Physicians in Germany are obliged to report ADR. A substantial proportion of ADR, however, is not reported because it is deemed to be either too well known or the association between the drug and the adverse effect is too doubtful. In some cases, histopathological findings are needed to determine the diagnosis of ADR. Accordingly, physicians should inform the pathologist whether an ADR is suspected and which drugs may be responsible.

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