Translational studies on a ready-to-use intramuscular injection of penethamate for bovine mastitis

Bovine mastitis caused by bacterial infections of the mammary gland (udder) of dairy cows is a costly pathology for the dairy industry due to direct and indirect losses in production. Penethamate, a pro-drug of benzylpenicillin, is used by intramuscular injection (IM). The existing products are powders which must be reconstituted in water-for-injection and this presents difficulties in the field. Penethamate is too unstable to be formulated as an aqueous formulation but a chemically stable suspension formulation was possible in certain oils; however, some literature suggests that such formulations would have unacceptable prolonged release. The translational research proceeded iteratively from lab to the target species, rather than via laboratory animal trials. Pilot studies in cows suggested that some oily suspensions would give concentrations of benzylpenicillin, (in both blood and milk) comparable with those of the reconstituted product. A physicochemical screen and a low level in vitro-in vivo correlation (IVIVC) was cautiously used to guide selection of formulations for subsequent animal trials which have resulted in a lead formulation for good laboratory practices (GLP), good clinical practices (GCP) studies.