Disposition and immunogenicity of penicillin in the rabbit

The immunogenicity, disposition and irreversible protein binding of benzylpenicillin (BP) were studied in male New Zealand White rabbits. There was an increase in IgG anti-benzylpenicilloyl (BPO) antibody activity, as detected by enzyme-linked immunosorbent assay (ELISA) following daily intramuscular administration (for 4 consecutive days) of BP (2.7 and 1.6 mmol/kg) freshly dissolved in 0.15 M NaCl. Antibody activity reached a maximum approximately 14 days after the last injection. There was a smaller immune response when a dose of 270 mumol/kg was administered. The specificity of the IgG antibody response for the BPO determinant was confirmed by inhibition of binding by BPO-aminocaproate. [3H]BP, administered intravenously to rabbits at a dose of 2.7 mmol/kg was rapidly cleared from plasma, and unchanged BP was not detected at 1 h. After 3 h, irreversible binding accounted for less than 0.004% of the dose bound per milliliter of plasma, and this represented all the radioactivity present in plasma at this time. Covalent binding of BP to plasma proteins, in vitro, after 3 h was of the same magnitude for rabbit, rat and human plasma. Therefore, BP can induce a specific antibody response in the rabbit in contrast to the lack of immunogenicity observed previously in the rat.