Clavulanate-potentiated amoxycillin: in vitro antibacterial activity and oral bioavailability in calves |
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| Authors: | S SOBACK A BOR B KURTZ R PAZ G ZIV |
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| Institution: | Ministry of Agriculture, Kimron Veterinary Institute, Bet-Dagan, Israel |
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| Abstract: | The minimal inhibitory concentrations (MIC) of amoxycillin and clavulanate-potentiated amoxycillin (amoxycillin:clavulanic acid, 4:1 by weight) were compared for 171 Salmonella, 170 Escherichia coli, and 32 Pasteurella isolates recovered from infected neonatal calves. In the presence of clavulanic acid, the MIC of amoxycillin was reduced to levels less than or equal to 12.5 micrograms/ml for all the Salmonella group B, all the Pasteurella, and for 12 out of the 44 E. coli isolates which were resistant to amoxycillin (MIC greater than or equal to 100.0 micrograms/ml). For isolates sensitive to amoxycillin (MIC less than or equal to 1.56 microgram/ml) there was no change in MIC values in the presence of clavulanic acid. A small proportion of Salmonella and E. coli isolates were resistant to clavulanate-potentiated amoxycillin. In a cross-over trial involving 10 preruminant (2 weeks old) calves, amoxycillin trihydrate and clavulanate-potentiated amoxycillin were administered orally at 10 mg/kg. An analysis of serum amoxycillin level data showed that the pharmacokinetic parameters t1/2ab, Cmax, t1/2 beta, AUC, Cp degree, and f' (estimated drug absorption ratio) were the same after treatment with amoxydrate and clavulanate-potentiated amoxycillin. Administration of clavulanate-potentiated amoxycillin and probenecid resulted in elevation and prolongation of serum amoxycillin levels. Computations showed that in preruminant calves serum amoxycillin concentrations sufficient to inhibit sensitive pathogens can be maintained by oral clavulanate-potentiated amoxycillin treatment at 10 mg/kg TID. At two times that dose rate serum drug concentrations capable of inhibiting 50% of all types of pathogens examined can be maintained.(ABSTRACT TRUNCATED AT 250 WORDS) |
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