Comparing the pharmacokinetics of a fourth generation cephalosporin in three different age groups of New Forest ponies

Abstract

SummaryReasons for performing study: To compare the pharmacokinetics of the fourth generation cephalosporin, cefquinome, in neonatal foals, 6-week-old foals and mature New Forest ponies in order to recommend appropriate dosage regimens for use of this drug. Methods: Cefquinome was administered i.v. at 1 mg/kg bwt twice a day (q. 12 h), 1 mg/kg bwt 3 times a day (q. 8 h) or 4.5 mg/kg bwt q. 12 h to each age group (n = 6). Plasma cefquinome concentrations were analysed using high-performance liquid chromatography combined with electrospray tandem mass spectrometry. Results: Both foal age groups had comparable pharmacokinetic data except for the volume of distribution at a steady-state (Vss), total body clearance (ClB) and mean residence time (MRT). Both ClB and MRT decreased as the age of the foals increased. Values of area under the curve increased, in a dose dependent manner, with significant increases for all age groups following administration of 4.5 mg/kg bwt q. 12 h. Total body clearance did not have comparable dose dependency. Conclusions: Cefquinome can be given at a dose of 1 mg/kg bwt q. 12 h for the treatment of infections caused by susceptible pathogens with MIC<0.125 mg/ml. A higher dose of 4.5 mg/kg bwt q. 12 h is recommended for the treatment of bacterial pathogens with minimal inhibitory concentration (MIC) 0.125-0.5 mg/ml Potential relevance: Commonly used dosing regimens should be critically evaluated in neonatal foals due to the higher volume of distribution of less lipophilic drugs in this age group.

Integration of PK/PD for dose optimization of Cefquinome against Staphylococcus aureus causing septicemia in cattle

“…Where T > MIC (in percent) is the time interval during which the drug plasma concentration is above or equal to the minimal inhibitory concentration (MIC) values; D is the planned dose; t 1/2 the terminal elimination half-life; and t is the dose interval (Smiet et al, 2012). …”

“…Cefquinome is the fourth generation cephalosporin, mainly used in veterinary medicine. This drug has been developed especially for use in veterinary medicine (Smiet et al, 2012; Papich, 2014), and is registered in many countries worldwide. Cefquinome has been used for the treatment of many diseases including acute mastitis, respiratory diseases, food rot in cattle, calf septicemia, metritis-mastitits-agalactia syndrome in sows, foal septicemia and respiratory diseases in horses (Uney et al, 2011; Liu et al, 2012; Dumka et al, 2013; Shan et al, 2014).…”

Plasma and synovial fluid pharmacokinetics of cefquinome following the administration of multiple doses in horses

“…The multiple‐dose kinetics of CFQ indicated that the t 1/2 λz ranged from 2.10 h to 2.41 h, which was similar to the previously reported values for CFQ in horses (Allan & Thomas, ; CVMP, ; Winther et al ., ; Smiet et al ., ). The mean MRT values ranged from 1.47 to 2.57 h, which were similar to previously reported values for CFQ in horses (Smiet et al ., ). However, the MRT was slightly shorter than the t 1/2 λz of all dose groups.…”

“…Previous studies have described the pharmacokinetics of CFQ following the i.v. administration of both single (0.5–2 mg/kg, Allan & Thomas, ; CVMP, ; 1 mg/kg, Winther et al ., ; 4.5 mg/kg, Smiet et al ., ) and multiple (a total of 3 doses of 1 mg/kg at 8‐h intervals and 2 doses of 1 mg/kg at 12‐h intervals; Smiet et al ., ) doses in horses. These studies have not reported adverse reactions of horses to CFQ.…”

Allometric analysis of the pharmacokinetics of four cephalosporin antibiotics in mammals

“…Their pharmacokinetics is extensively studied in a number of animal species after different routes of administration. These drugs have a similar distribution and differ mainly in elimination phase and especially in elimination rates depending on the species and age (Smiet et al, 2012). Considerable variations are registered after oral absorption.…”