Pharmacology: Pharmacodynamics: Benzathine penicillin is a depot preparation of benzylpenicillin with the same mode of action as that benzylpenicillin. The penicillin nucleus consist of thiazolidine ring connected to β-lactam ring to which is attached a side chain. The β-lactam ring plays an important role in the antibacterial activity of β-lactam antibiotics. It can be opened by β-lactamase produced by enzyme-producing organisms. As soon as the β-lactam ring is opened by the β-lactamase the hydrolysed penicillin is inactivated. The side-chain determines most of the pharmacological properties as well as the characteristics of the antimicrobial activity penicillins. Penicillin kills bacteria by interfering with the synthesis of the bacteria cell wall. This is composed of peptidoglycan which is a heteropolymeric structure that provides the cell wall with mechanical stability. The final stage in the synthesis of peptidoglycan involves the completion of the cross-linking between the terminal glycine residue of the pentaglycine bridge and the fourth residue of the pentapeptide (d-alanine). The transpeptidase that performs this step is inhibited by penicillins and cephalosphorins, the β-lactam ring of which acts as an analogue of acyl-d-ananyl-d-alanine. As a result the bacteria cell wall is weakened and then ruptures. Recently it was proved that there are penicillin-binding-proteins (PBPs) in the cell envelope of bacteria which are the targets for β-lactam antibiotics.
Pharmacokinetics: Absorption and serum levels: Benzathine penicillin is stable in the presence of gastric juice, but not absorption from the gastro-intestinal tract. Benzathine penicillin is very slowly absorbed from intramuscular deport. It is hydrolysed to benzylpenicillin and produces sustained low levels of penicillin in the blood for an average 4 weeks period. A dose of 1.2 million units given intramuscularly produces a concentration in plasma of 150/u/ltr on the first and 30u/ltr on the fourteenth day. After a single injection of 2.4 million units of benzathine penicillin in young subjects, the mean serum penicillin concentration was 340u/ltr after hours.
Distribution: Approximately 60% of benzylpenicillin is bond to serum proteins. The drug is distributed throughout the body tissues in widely varying amounts. Highest levels are found in kidneys with lesser amounts in the liver skin and in intestines. Benzylpenicillin penetrates into all other tissues and spinal fluid to a lesser degree. With normal kidney function, the drug is excreted rapidly by tubular excretion. In neonates and young infants and in individuals with impaired kidney function, excretion is completely delayed.
Metabolism of excretion: Benzathine penicillin is partially metabolised to inactive penicilloic acid in the liver in the same manner as is benzylpenicillin. Once benzylpenicillin is released from repository forms, it is excreted by the kidney. About 70 to 80% of injected penicillin can be recovered in the urine and about 20% are excreted by the biliary system into gastrointestinal tract. Because absorption in to the blood from injection site is continued over a long period, the excretion of active penicillin in the urine is prolonged. Studies have revealed urinary excretion persisting from 84 days to more than 100 days. It seems reasonable that benzathine penicillin persists for a longer time in tissues than in the blood stream.