Determination of cefquinome in pig plasma and bronchoalveolar lavage fluid by high‐performance liquid chromatography combined with electrospray ionization mass spectrometry

Maes, An; Meyns, Tom; Sustronck, Bart; Maes, Dirk; Backer, Patrick De; Croubels, Siska

doi:10.1002/jms.1199

Cited by 18 publications

(14 citation statements)

References 7 publications

(16 reference statements)

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“…To the authors’ knowledge, only two methods have been described for the determination of CEQ in serum, including microbiology assay (Block et al. , 2005) and liquid chromatography combined with electrospray ionization mass spectrometry (Maes et al. , 2007).…”

Section: Discussionmentioning

confidence: 99%

“…To the authors' knowledge, only two methods have been described for the determination of CEQ in serum, including microbiology assay (Block et al, 2005) and liquid chromatography combined with electrospray ionization mass spectrometry (Maes et al, 2007). According to the results of the methodology study in this report, a sensitive and routine HPLC-UV method for the determination of CEQ in serum was developed and applied to study the pharmacokinetic profiles of CEQ in piglets.…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics and bioavailability of cefquinome in healthy piglets

et al. 2008

Vet Pharm & Therapeutics

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A study on bioavailability and pharmacokinetics of cefquinome in piglets was conducted after intravenous (i.v.) and intramuscular (i.m.) administrations of 2.0 mg/kg of body weight, respectively. Plasma concentrations were measured by high-performance liquid chromatography assay with UV detector at 268-nm wavelength. Plasma concentration-time data after i.v. administration were best fit by a two-compartment model. The pharmacokinetic values were distribution half-life 0.27 +/- 0.21 h, elimination half-life 1.85 +/- 1.11 h, total body clearance 0.26 +/- 0.08 L/kg.h, area under curve 8.07 +/- 1.91 microg x h/mL and volume of distribution at steady state 0.46 +/- 0.10 L/kg. Plasma concentration-time data after i.m. administration were also best fit by a two-compartment model. The pharmacokinetic parameters were distribution half-life 0.88 +/- 0.42 h, elimination half-life 4.36 +/- 2.35 h, peak concentration 4.01 +/- 0.57 microg/mL and bioavailability 95.13 +/- 9.93%.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and bioavailability of cefquinome in healthy piglets

et al. 2008

Vet Pharm & Therapeutics

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“…Cefquinome (formerly HR 111V) is a fourth-generation cephalosporin developed solely for veterinary use. It displays antimicrobial activities in vitro and in vivo against a broad spectrum of Gram-positive and Gram-negative bacterial species, including methicillin-resistant and methicillin-susceptible S. aureus, and it is considered to be highly stable against ␤-lactamases encoded by chromosomes and genes on plasmids (7)(8)(9).…”

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confidence: 99%

Pharmacodynamics of Cefquinome in a Neutropenic Mouse Thigh Model of Staphylococcus aureus Infection

Wang

Ding

et al. 2014

Antimicrob Agents Chemother

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bCefquinome is a cephalosporin with broad-spectrum antibacterial activity, including activity against Staphylococcus aureus. The objective of our study was to examine the in vivo activity of cefquinome against S. aureus strains by using a neutropenic mouse thigh infection model. Cefquinome kinetics and protein binding in infected neutropenic mice were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In vivo postantibiotic effects (PAEs) were determined after a dose of 100 mg/kg of body weight in mice infected with S. aureus strain ATCC 29213. The animals were treated by subcutaneous injection of cefquinome at doses of 2.5 to 320 mg/kg of body weight per day divided into 1, 2, 3, 6, or 12 doses over 24 h. Cefquinome exhibited time-dependent killing and produced in vivo PAEs at 2.9 h. The percentage of time that serum concentrations were above the MIC (%T >MIC ) was the pharmacokinetic-pharmacodynamic (PK-PD) index that best described the efficacy of cefquinome. Subsequently, we employed a similar dosing strategy by using increasing total cefquinome doses that increased 4-fold and were administered every 4 h to treat animals infected with six additional S. aureus isolates. A sigmoid maximum effect (E max ) model was used to estimate the magnitudes of the ratios of the %T that the free-drug serum concentration exceeded the MIC (%T >fMIC ) associated with net bacterial stasis, a 0.5-log 10 CFU reduction from baseline, and a 1-log 10 CFU reduction from baseline; the respective values were 30.28 to 36.84%, 34.38 to 46.70%, and 43.50 to 54.01%. The clear PAEs and potent bactericidal activity make cefquinome an attractive option for the treatment of infections caused by S. aureus. Staphylococcus aureus, especially methicillin-resistant S. aureus (MRSA), is an important human pathogen that is also an emerging concern in veterinary medicine and animal agriculture. All known mammalian species, including common laboratory rodent and rabbit species, are susceptible to colonization with S. aureus. MRSA has been shown to have a prevalence of 39% and 24.9% in pigs in the Netherlands (1) and Canada (2), respectively, and 28% in veal calves in the Netherlands (3). A Canadian study identified MRSA in 6.3% of ground pork and 5.6% of ground beef but in 32% and 45% of positive pork and beef samples, respectively (4). Some samples of commercially sold meat products in Japan were also found to harbor MRSA strains (5). Because of its ability to colonize a wide range of species, S. aureus can be readily transmitted from one species to another, including from humans to animals and vice versa. Moreover, a majority of S. aureus isolates are resistant to various antimicrobial agents (6), and thus, there are limited antimicrobial options for treatment; accordingly, there is a growing need for more potent antimicrobials to attack these resistant pathogens. Cefquinome (formerly HR 111V) is a fourth-generation cephalosporin developed solely for veterinary use. It displays antimicrobial activities in vitro and in vivo agains...

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“…The extraction procedure was modified from a previously published method (Maes et al, 2007). A 500 lL aliquot of HPLC grade acetonitrile was added to 500 lL thawed plasma of each 1 Baotao Liu and Chiye Zhang contributed equally to this work.…”

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confidence: 99%