Pharmacokinetics of Cefovecin in Cynomolgus Macaques (Macaca fascicularis), Olive Baboons (Papio anubis), and Rhesus Macaques (Macaca mulatto)

Journal Article · Sun May 01 04:00:00 EDT 2011 · Journal of the American Association for Laboratory Animal Science

OSTI ID:1028062

Raabe, Brigitte M; Lovaglio, Jamie A; Grover, GScott; Brown, Scott A; Boucher, Joseph F; Yuan, Yang; Civil, Jacqueline R; Gillhouse, Kimberly A; Stubbs, Makeida N; Hoggatt, Amber F; Halliday, Lisa C; Fortman, Jeffrey D

Cefovecin sodium is a long-acting, third-generation, cephalosporin antibiotic approved for the treatment of skin infections in dogs and cats. The pharmacokinetic properties of cefovecin were evaluated in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatto) by using a single-dose (8 mg/kg SC) dosing regimen. Plasma cefovecin concentrations were determined by using ultra-performance liquid chromatography with tandem mass spectrometry, and a noncompartmental model was used to determine pharmacokinetic parameters. The half-life of cefovecin was 4.95 {+-} 1.47 h in cynomolgus macaques, 9.17 {+-} 1.84 h in olive baboons, and 8.40 {+-} 2.53 h in rhesus macaques. These values are considerably lower than the half-lives previously published for dogs (133 h) and cats (166 h). The extended half-life of cefovecin in dogs and cats is speculated to be due to active reabsorption of drug in the kidney tubules because plasma clearance is well below the normal glomerular filtration rate. In nonhuman primates, renal clearance rates approximated plasma clearance rates, suggesting that active renal reabsorption of cefovecin does not occur in these species. The pharmacokinetic properties of cefovecin in nonhuman primates are vastly different from the pharmacokinetic properties in dogs and cats, precluding its use as a long-acting antibiotic in nonhuman primates. This study highlights the importance of performing pharmacokinetic studies prior to extralabel drug usage.

• Research Organization: Pacific Northwest National Laboratory (PNNL), Richland, WA (US)
• Sponsoring Organization: USDOE
• DOE Contract Number: AC05-76RL01830
• OSTI ID: 1028062
• Report Number(s): PNNL-SA-81229
• Journal Information: Journal of the American Association for Laboratory Animal Science, Journal Name: Journal of the American Association for Laboratory Animal Science Journal Issue: 3 Vol. 50
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBIOTICS
BABOONS
BLOOD-PLASMA CLEARANCE
CHROMATOGRAPHY
FILTRATION
HALF-LIFE
KIDNEYS
MACACUS
MASS SPECTROSCOPY
OLIVES
PLASMA
PRIMATES
RENAL CLEARANCE
SODIUM
TUBULES