Pharmacokinetics of anti-Pseudomonas hyperimmunoglobulin after single intravenous administration in healthy subjects

Abstract

This is the first report of the pharmacokinetics of an intravenous hyperimmunoglobulin investigated by assays measuring functional activity. The anti-Pseudomonas hyperimmunoglobulin had previously been shown to be specific and effective in Pseudomonas aeruginosa infectious challenge models when given prophylactically to laboratory animals. In order to facilitate calculation of effective dosage regimes of hyperimmunoglobulin in patients, the pharmacokinetics of 15 g of an anti-Pseudomonas hyperimmunoglobulin was investigated after intravenous administration to six healthy male volunteers. The pharmacokinetics were followed in serum for sixteen days by four assays measuring total IgG, ELISA titre to Pseudomonas serotype 6 or a multivalent Pseudomonas vaccine, and mouse protection against infectious challenge. The increase of ELISA titre and mouse protective ability was modest, being approximately twice that of normal pooled serum. The half-life of the biologically active antibody as measured by the mouse protection assay was about seven days, and the half-life of total anti-Pseudomonas antibodies as measured by ELISA varied greatly between individuals (8–33 days). These results suggest that previous trials of fixed dose hyperimmunoglobulin in patients may have been ineffective owing to inadequate dosage regimens.