title: Population pharmacokinetic analysis of blood concentrations of robenacoxib in dogs with osteoarthritis.
abstract: The purpose of this analysis was to investigate whether the recommended daily dosage of 1-2mg/kg robenacoxib provides consistent exposure when administered to dogs with chronic osteoarthritis (OA), and the need for dose adjustment in special patient populations. Data from three prospective, multi-center field studies in 208 OA dogs were analyzed using non-linear mixed effects modeling. A model based assessment was performed with stepwise inclusion and exclusion of population characteristics to explain between-subject variability, and assess the according necessity for dose adjustment. Only the influence of bodyweight on both apparent clearance and volume were found to be significant (p<0.01). No significant influence of sex, age and breed, or kidney and liver variables was identified in this representative sample of OA dogs. The population pharmacokinetic analysis performed showed that the 1-2mg/kg dosage chosen provided consistent robenacoxib exposure in a wide range of canine patients. No other dose adjustment seems necessary.
authors.affiliation: Novartis Pharma AG, Modeling & Simulation, CH-4002 Basel, Switzerland. martin.fink@novartis.com
authors.forename: M
authors.initials: M
authors.lastname: Fink
authors.forename: I
authors.initials: I
authors.lastname: Letellier
authors.forename: M
authors.initials: M
authors.lastname: Peyrou
authors.forename: J P
authors.initials: JP
authors.lastname: Mochel
authors.forename: M
authors.initials: M
authors.lastname: Jung
authors.forename: J N
authors.initials: JN
authors.lastname: King
authors.forename: P
authors.initials: P
authors.lastname: Gruet
authors.forename: J M
authors.initials: JM
authors.lastname: Giraudel
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000097:blood* / Q000493:pharmacokinetics; D001835:Body Weight; D002908:Chronic Disease; D004159:Diphenylamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D004283:Dog Diseases / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D008297:Male; D010003:Osteoarthritis / Q000097:blood / Q000188:drug therapy / Q000662:veterinary*; D010648:Phenylacetates / Q000097:blood* / Q000493:pharmacokinetics; D012737:Sex Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010648:Phenylacetates; D004159:Diphenylamine; C551524:robenacoxib
keywords: AUC; BLQ; COX; COXIB; Dog; EBEs; FOCE; IIV; IOV; LLOQ; NSAID; OA; OFV; Population pharmacokinetics; RSE; Robenacoxib; area under the curve; below limit of quantification; cyclooxygenase; empiricial Bayes estimates; first order conditional estimation method; inter-individual variability; inter-occasion variability; lower limit of quantification; non-steroidal anti-inflammatory drug; objective function value; osteoarthritis; relative standard error