Pharmacokinetics of Amoxicillin in the Cat

Abstract

The pharmacokinetics and plasma protein binding of amoxicillin in cats has not been thoroughly investigated. In a single-group sequential designed experimental study, amoxicillin was administered to six healthy cats intravenously, orally, and subcutaneously. Repeated blood samples were drawn after each administration, and amoxicillin concentrations were determined using High Performance Liquid Chromatography coupled to Triple Quadrupole Mass Spectrometry. Plasma amoxicillin data were subjected to population pharmacokinetic analysis, and pharmacokinetic parameters were estimated. The population clearance was 0.18 L/h∙kg, the volume of the central compartment was 0.12 L/kg, the highly perfused compartment was 0.009 L/kg, and the poorly perfused compartment was 0.002 L/kg. The bioavailability was 33% and 69% after oral and subcutaneous administration, respectively. After subcutaneous administration of a slow-release formulation, there was absorption rate-limited pharmacokinetics. The plasma protein binding was 0%-24%. The results increase the understanding of the amoxicillin pharmacokinetics in cats. Further studies combining the results with pharmacodynamic data and in silico simulations are warranted.

Keywords: antibiotic; disposition; feline; penicillin; plasma concentration.

FIGURE 1

Semi logarithmic spaghetti plot showing observed (symbols) and model predicted (lines) plasma amoxicillin concentration‐time courses after 10 mg/kg intravenously (left plot, IV), 10 mg/kg orally (middle plot, PO) and 15 mg/kg subcutaneously (right plot, SC) to six cats. For one cat, the intravenous dose was injected perivascular so intravenous data from this cat was excluded.

FIGURE 2

Godness of fit plots showing observed concentrations VS predicted concentrations after intravenous (IV) administration, oral (PO) administration and subcutaneous administration (SC) of amoxicillin to six cats. Filled black circles represent observed data. The solid line represent the line of unity (observation = prediction).

FIGURE 3

Goodness of fit plots showing Individual weighted residuals versus time and predicted concentration after intravenous (IV) administration, oral (PO) administration and subcutaneous administration (SC) of amoxicillin to six cats.

FIGURE 4

Visual predictive check after intravenous (IV) administration, oral (PO) administration and subcutaneous administration (SC) of amoxicillin to six cats. The solid lines represents the 10th, 50th, and 90th empirical percentile, respectively. The dark grey shaded areas are the 10th and the 90th prediction interval and the light grey shaded area is the median prediction interval.