Pharmacokinetic parameters for single- and multi-dose regimens for subcutaneous administration of a high-dose ceftiofur crystalline-free acid to neonatal foals.
The objective of this study was to determine the pharmacokinetics of single- and multi-dose ceftiofur crystalline-free acid (CCFA) administered subcutaneously at a dose of 13.2 mg/kg to 12 neonatal foals 1-3 days of age. Six foals received a single subcutaneous dose, while 6 additional foals received 4 doses of CCFA at 48-h intervals. Blood samples were collected at pre-determined times following drug administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured using high-performance liquid chromatography. Following single-dose administration of CCFA, the mean ± standard deviation maximum observed plasma concentration was 3.1 ± 0.6 μg/mL and observed time to maximal plasma concentration was 14.0 ± 4.9 h. Following multi-dose administration of CCFA, the mean ±standard deviation times above CFAE concentrations of ≥0.5 μg/mL and ≥2.0 μg/mL were 192.95 ± 15.86 h and 78.80 ± 15.31 h, respectively. The mean ± standard deviation area under the concentration vs time curve (AUC0→∝) was 246.2 ± 30.7 h × μg/mL and 172.7 ± 27.14 h × μg/mL following single- and multi-dose CCFA administrations, respectively. Subcutaneous administration of CCFA at 13.2 mg/kg in neonatal foals was clinically well- tolerated and resulted in plasma concentrations sufficient for the treatment of most bacterial pathogens associated with neonatal foal septicemia. Multi-dose administration of four doses at dosing interval of 48 h between treatments maintains appropriate therapeutic concentrations in neonatal foals.
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
N
N
Pusterla
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
T L
TL
Hall
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
S E
SE
Wetzlich
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
G
G
Monmaney
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
J R
JR
Collier
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
J A
JA
Hill
Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California, Davis, CA, USA.
L A
http://orcid.org/0000-0003-1823-7420
LA
Tell
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D003692:Delayed-Action Preparations; D004334:Drug Administration Schedule; D005260:Female; D006736:Horses / Q000378:metabolism; D007279:Injections, Subcutaneous / Q000662:veterinary; D008297:Male
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D003692:Delayed-Action Preparations; C053503:ceftiofur