title: Pharmacokinetics of cefovecin in cynomolgus macaques (Macaca fascicularis), olive baboons (Papio anubis), and rhesus macaques (Macaca mulatta).
abstract: 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 mulatta) 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.
authors.affiliation: Biological Resources Laboratory, University of Illinois at Chicago, Chicago, Illinois, USA. bmraabe@wisc.edu
authors.forename: Brigitte M
authors.initials: BM
authors.lastname: Raabe
authors.forename: Jamie
authors.initials: J
authors.lastname: Lovaglio
authors.forename: G Scott
authors.initials: GS
authors.lastname: Grover
authors.forename: Scott A
authors.initials: SA
authors.lastname: Brown
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Boucher
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Civil
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Gillhouse
authors.forename: Makeida N
authors.initials: MN
authors.lastname: Stubbs
authors.forename: Amber F
authors.initials: AF
authors.lastname: Hoggatt
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Halliday
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Fortman
mesh_terms: D000818:Animals; D000830:Animals, Laboratory / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005919:Glomerular Filtration Rate; D006207:Half-Life; D008252:Macaca fascicularis / Q000378:metabolism*; D008253:Macaca mulatta / Q000378:metabolism*; D008297:Male; D008992:Monkey Diseases / Q000188:drug therapy / Q000517:prevention & control; D048530:Papio anubis / Q000378:metabolism*; D012871:Skin Diseases / Q000188:drug therapy / Q000517:prevention & control / Q000662:veterinary; D013045:Species Specificity
chemical_list: D000890:Anti-Infective Agents; D002511:Cephalosporins; C516253:cefovecin