Pharmacology of procaine in the horse: evidence against the existence of a "procaine - penicillin" complex.

It has recently been suggested that procaine penicillin existed in solution in vitro and in vivo as a "procaine - penicillin" complex rather than as dissociated ions. In vivo, this complexed procaine was considered unavailable for hydrolysis by plasma esterases or for interaction with pharmacologic receptors for procaine. When procaine penicillin was intramuscularly given to horses, about 90% of the procaine in blood drawn from these horses was split at the same rate as authentic procaine or procaine penicillin added to equine blood in vitro. In vitro, procaine and procaine penicillin partitioned similarly from aqueous medium at physiologic pH into several organic solvents and were split at the same rate by blood or plasma esterases. Experiments on the time course of the partitioning of procaine from procaine penicillin into benzene showed no evidence for the existence of a "procaine - penicillin" complex within seconds after procaine penicillin was added to aqueous medium. Thin layer chromatography in 2 dimensions also yielded no evidence for the existence of this postulated complex. These results show no evidence in support of the "procaine - penicillin" hypothesis and argue against the physical and pharmacologic and forensic implications of this hypothesis.