title: Pharmacokinetics of Cefovecin in squirrel monkey (Saimiri sciureus), rhesus macaques (Macaca mulatta), and cynomolgus macaques (Macaca fascicularis).
abstract: Cefovecin sodium is a third-generation broad-spectrum cephalosporin antibiotic licensed for the treatment of skin infections in cats and dogs. The objective of our study was to assess whether its pharmacokinetic profile in squirrel monkey, rhesus macaques, and cynomolgus macaques was similar to that of dogs. Plasma levels were determined by using protein precipitation followed by liquid chromatography tandem mass spectrometry. After subcutaneous dosing at 8 mg/kg, the plasma terminal half-life of cefovecin was substantially shorter in the nonhuman primates (2.6 to 8.0 h) than in dogs (102 h). The total plasma exposure (AUC(0-96h)) was 10- to 40-fold lower in nonhuman primate species. In cynomolgus macaques, cefovecin showed a similar subcutaneous bioavailability (82% compared with 100%) and volume of distribution (0.16 compared with 0.12 L/kg) as compared to dogs; however, the plasma clearance of cefovecin was 20-fold higher. Cefovecin susceptibility testing and minimum inhibitory concentrations were not established for clinical isolates in nonhuman primates. However, if the minimum inhibitory concentrations of cefovecin for various nonhuman primates pathogens are in the same range as those observed for canine pathogens, our results suggest that cefovecin used at the same dosing regimen and frequency prescribed for the dogs will be ineffective and that increases in dose or frequency (or both) may be required.
authors.affiliation: Drug Metabolism and Pharmacokinetics, Merck Frosst Centre for Therapeutic Research, Merck Frosst Canada, Kirkland, Québec, Canada. rpapp000@sympatico.ca
authors.forename: Robert
authors.initials: R
authors.lastname: Papp
authors.forename: Aleksandar
authors.initials: A
authors.lastname: Popovic
authors.forename: Nancy
authors.initials: N
authors.lastname: Kelly
authors.forename: Richard
authors.initials: R
authors.lastname: Tschirret-Guth
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002511:Cephalosporins / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D004283:Dog Diseases / Q000188:drug therapy; D004285:Dogs / Q000378:metabolism*; D006207:Half-Life; D007279:Injections, Subcutaneous / Q000662:veterinary; D008252:Macaca fascicularis / Q000097:blood / Q000378:metabolism*; D008253:Macaca mulatta / Q000097:blood / Q000378:metabolism*; D008297:Male; D012453:Saimiri / Q000097:blood / Q000378:metabolism*; D017192:Skin Diseases, Bacterial / Q000188:drug therapy / Q000662:veterinary; D013045:Species Specificity
chemical_list: D000900:Anti-Bacterial Agents; D002511:Cephalosporins; C516253:cefovecin