Clavulanate‐potentiated amoxycillin: in vitro antibacterial activity and oral bioavailability in calves

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Abstract
Soback, S., Bor, A., Kurtz, B., Paz, R. & Ziv, G. Clavulanate‐potentiated amoxycillin: in vitro antibacterial activity and oral bioavailability in calves. J. vet. Pharmacol. Therap.10, 105–113.The minimal inhibitory concentrations (MIC) of amoxycillin and clavulanate‐potentiated amoxycillin (amoxycillinxlavulanic 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 ≥ 12.5 μg/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 ≥ 100.0 μg/ml). For isolates sensitive to amoxycillin (MIC ≥ 1.56 μg/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 t½ab, Cmax, t½β, AUC, Cpo, 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. Amoxycillin was apparently inactivated by the g.i. contents of early ruminant (6 weeks old) calves as oral clavulanate‐potentiated amoxycillin treatment at 20 mg/kg did not result in serum drug levels of potential therapeutic value.