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Pharmacological particulars
Pharmacotherapeutic group: Beta-lactamase sensitive penicillins.
ATCvet code: QJ01CE90
Pharmacodynamic properties
In aqueous environments, penethamate is hydrolysed to form benzylpenicillin and diethylaminoethanol. The mode of action of benzylpenicillin is by prevention of cell wall synthesis during bacterial cell growth and its activity is primarily bactericidal and time-dependent. The antimicrobial spectrum of the active substance corresponds to that of benzylpenicillin which is active against beta-lactamase negative Streptococcus agalactiae, Streptococcus dysgalactiae, Streptococcus uberis and Staphylococcus aureus. In 2011 the MIC90 values for penicillin in Sweden were 0.12 μg/ml for S. aureus, 0.12 μg/ml for S. dysgalactiae and 0.12 μg/ml for S. uberis. In 2012 the MIC90 values for penicillin in Germany were 0.031 μg/ml for S. agalactiae, 0.015 μg/ml for S.dysgalactiae and 0.125 μg/ml for S. uberis. In 2013 the MIC90 values for penicillin in Switzerland were 1.0 μg/ml for S. aureus, ≤0.12 μg/ml for S. dysgalactiae and ≤0.12 μg/ml for S. uberis. EUCAST reports an Epidemiological Cut OFF value (ECOFF) of 0.125 μg/ml for S. aureus and an ECOFF of 0.125 μg/ml for S. agalactiae. For S. dysgalactiae and S. uberis no ECOFF values are determined.
The most frequent mechanism of resistance is producing beta-lactamases (more specifically penicillinase especially in S. aureus), which break the beta-lactam ring of penicillins, making them inactive.
Pharmacokinetic properties
Penethamate hydriodide is the diethylaminoethyl ester of penicillin, which contains an acidic carboxylic acid grouping. The ester is non-iodised and has high lipid solubility. The major pharmacokinetic properties of penethamate hydriodide are its rapid absorption with high bioavailability and rapid metabolism in vivo to penicillin, the therapeutically active molecule. In circulation it is rapidly hydrolysed to diethylaminoethanol and penicillin, with approximately 90% existing as penicillin. The parent compound readily penetrates into milk, as a consequence of its high lipid solubility. In milk, it is hydrolysed to penicillin and this maintains the plasma/milk concentration gradient for the parent compound. This is a mechanism of passive diffusion from a fluid of pH 7.4 to a more acid pH in milk. With a pKa value of 2.7, penicillin is highly ionised in both plasma and milk. The pH gradient between plasma (pH 7.4) and milk (pH 6.6-6.8) is reduced in mastitis but nevertheless is not abolished.
Cmax is 682 ng/mL, AUClast is 7770 h*ng/mL and elimination half-life is 6.84 hours. Apart from excretion in the milk, benzylpenicillin is also excreted via the kidneys.