Disposition and Immunogenicity of Penicillin in the Rabbit

Abstract

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 μmol/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 < 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.

Allergic reactions to drugs: current concepts and problems

“…5% in that rat [30]). This represents an average hapten density (molar ratio of drug to protein) on circulating plasma proteins of 0-2 compared to only 0 03 in the rat after similar doses of the drug [32]. Interestingly, fresh BP without adjuvant does induce an IgG anti-BPO antibody response in the rabbit [32] athough this was not the case in the rat (see above).…”

“…This represents an average hapten density (molar ratio of drug to protein) on circulating plasma proteins of 0-2 compared to only 0 03 in the rat after similar doses of the drug [32]. Interestingly, fresh BP without adjuvant does induce an IgG anti-BPO antibody response in the rabbit [32] athough this was not the case in the rat (see above). This species difference in drug immunogenicity may in part reflect the greater extent of conjugation to proteins seen in the rabbit, but undoubtedly genetic differences in immunological responsiveness are also important.…”

“…Studies with rabbits have shown that in this species free BP is cleared very rapidly from the circulation, and 3 hr after intravenous administration 100% of circulating drug is covalently bound to plasma proteins [32] (c.f. 5% in that rat [30]).…”