Pharmacokinetics of the amoxicillin–clavulanic acid combination after intravenous and oral administration in cats

Abstract

The pharmacokinetic properties of amoxicillin (AMX) and clavulanic acid (CLV) were studied in healthy cats following single intravenous and oral dosage of 10 mg/kg of AMX and 2.5 mg/kg of CLV. The drug concentrations in plasma were determined by a high‐performance liquid chromatographic–tandem mass spectrometry (LC‐MS‐MS) method validated for canine plasma and further subjected to noncompartmental analysis. After intravenous injection, no significant difference (p > 0.05) was found in the volume of distribution of these two compounds. In addition, AMX and CLV were both rapidly eliminated from plasma with a clearance of 0.453 and 0.921 L hr−1 kg−1, respectively; however, a quicker elimination was observed for CLV (p < 0.01). After oral administration, both drugs were characterized by rapid absorption with an absorption half‐life of 1.10 and 0.70 hr for AMX and CLV, respectively. Significant differences were observed between their absorption rates (p < 0.05). However, the oral bioavailabilities of AMX and CLV (75.57% and 98.15%, respectively) were not statistically different (p > 0.05). A total intravenous or oral dose at 12.5 mg/kg of AMX and CLV (4:1) is predicted to be effective for treating those bacterial species isolated from cats with a minimum inhibitory concentration (MIC) of ≤0.25 μg/ml for 12 hr, based on a time above the MIC (T > MIC) of 40%.

Mass spectrometric identification and quantification of the antibiotic clavulanic acid in broiler chicken plasma and meat as a necessary analytical tool in finding ways to increase the effectiveness of currently used antibiotics in the treatment of broiler chickens

“…Extraction procedure with acetonitrile precipitation proved to be the most effective. It is in accordance with other publications [ 6 , 7 , 9 , 10 ] in which the authors stated recovery more than 90%. Firstly, we tried to concentrate the final sample solution by nitrogen steam evaporation.…”

“…LLOQ was 25.28 μg·L −1 and the recovery was in the range of 47–51%. For animal plasma, Reyns et al [ 9 ] developed a method for clavulanic acid determination in calf plasma and Yang et al in cat plasma [ 10 ]. Sample preparation included acetonitrile precipitation followed by dichloromethane extraction and syringe filtration, respectively.…”

The bioavailability and pharmacokinetics of an amoxicillin–clavulanic acid granular combination after intravenous and oral administration in swine

“…As CA can protect AMX from destruction by beta‐lactamase enzymes, this combination has been widely used in human and veterinary medicine (White et al., 2004). The pharmacokinetics of AMX‐CA combination has been studied in goats, broiler chickens, koalas, pigs and cats (Carceles et al., 1995; Jerzsele et al., 2009; Kimble et al., 2019; Reyns et al., 2007; Yang et al., 2019), which was characterized by rapid absorption, short half‐life and rapid clearance after administration. However, the pharmacokinetics of an AMX‐CA granular formulation in pigs has not been thoroughly investigated.…”

“…The concentrations of AMX and CA in swine plasma were determined using high‐performance liquid chromatographic‐tandem mass spectrometry. The samples were extracted using acetonitrile and then analysed after centrifugation as described previously (Sinphithakkul et al., 2016; Yang et al., 2019).…”

“…The F of CA in our study was slightly lower than that reported previously, indicating that the absorption degree of CA following administration varied greatly in pigs (Reyns et al., 2007). Moreover, the bioavailability of AMX‐CA combination in pigs was lower than that in cats (AMX: 76.57%; CA: 98.15%, tablet) and in turkeys (AMX: 60.2%; CA: 60.7%, powder) at the same dose of 12.5 mg/kg (Jerzsele et al., 2011; Yang et al., 2019).…”