Pharmacokinetic evaluation and mammary excretion of tamethicillin in the healthy goat.

We evaluated the pharmacokinetics and the mammary excretion of a new beta-lactam antibiotic derivative, the diethylaminoethyl ester of methicillin, commonly known as tamethicillin. Tamethicillin is a hydrolyzable weak basic ester (pro-drug) that is converted to methicillin in the body. Its pharmacokinetic profile compares favorably with that of methicillin. In this sense, tamethicillin had five times greater distribution volume than methicillin, and both its slow phase half-time (t 1/2) and elimination half-time (t 1/2 Kel) were clearly greater. In addition, our experimental studies on mammary excretion in the goat have demonstrated a better selectivity for the udder of tamethicillin as compared with methicillin. Results of 2 years of field experience show that tamethicillin can be considered a useful alternative for the treatment of mastitis in livestock, especially in mastitis due to beta-lactamase-producing Staphylococcus.

Concentrations of methicillin in blood, normal milk and mastitic milk of cows after intramuscular injection of methicillin and tamethicillin.

Tamethicillin (TAM) is a basic ester pro-drug of methicillin (MET) which is converted in the body by non-specific esterases to MET. Equal doses of MET and TAM were administered intramuscularly in a crossover trial involving four dairy cows. Acute mastitis was induced in each cow by infusing two quarters of the udder with Escherichia coli endotoxin 3 h before antibiotic administration. Peak serum MET concentrations after MET injection were significantly (P less than 0.001) higher than peak serum drug concentrations after TAM injection. The t1/2 of MET in serum after MET and TAM treatments were 18 min and 2 h, respectively. Normal milk MET concentrations during the first 8 h after TAM administration were significantly (P less than 0.05) higher than after MET treatment. Mastitic milk MET concentrations during the period 2-6 after MET injection were significantly (P less than 0.01) higher than after TAM administration. However, MET concentrations which were equal to or higher than the minimal inhibitory concentrations for penicillin G-resistant staphylococci were maintained in the mastitic milk for 8 h after treatment with MET and TAM.

Intramuscular treatment of subclinical staphylococcal mastitis in lactating cows with penicillin G, methicillin and their esters.

The relationship between antibiotic milk concentrations and bacteriological efficacy was investigated in groups of lactating cows with subclinical mastitis due to either penicillin G-sensitive or penicillin G-resistant Staphylococcus aureus. Treatments consisted of the intramuscular injection of procaine penicillin G, or its weak base ester penethamate hydriodide, and sodium methicillin, or its weak base ester tamethicillin. Antibiotics were administered once daily for 2 or 4 days at accepted dosages. After four daily, treatments with procaine penicillin G and penethamate hydriodide, infections were eliminated from 56.5% and 68.8%, respectively, of quarters infected with penicillin G-sensitive staphylococci, and from 14.3% and 7.7%, respectively, of quarters infected with penicillin G-resistant staphylococci. After four daily treatments with sodium methicillin and tamethicillin, infections were eliminated from 32.4% and 48.6%, respectively, of quarters infected with penicillin G-resistant staphylococci. The better efficacy of penethamate hydriodide and tamethicillin was considered to be linked to the higher milk drug concentrations obtained with these drugs as opposed to the lower concentrations measured in the milk after treatment with the parent drugs. Cure rates were generally higher after treatment for 4 days than after the 2-day course of therapy. Treatment efficacy decreased progressively with increasing age of the cows. Intramuscular treatment of subclinical staphylococcal mastitis in lactating cows can serve as a useful model for screening existing and new antibacterial agents and drug products intended for the parenteral treatment of clinical staphylococcal mastitis.