Population pharmacokinetic analysis of blood concentrations of robenacoxib in dogs with osteoarthritis

• Published in: Research in veterinary science Vol. 95; no. 2; pp. 580 - 587
• Main Authors: Fink, M., Letellier, I., Peyrou, M., Mochel, J.P., Jung, M., King, J.N., Gruet, P., Giraudel, J.M.
• Format: Journal Article
• Language: English
• Published: England Elsevier India Pvt Ltd 01.10.2013; Elsevier Limited
• Subjects: Age; analogs & derivatives; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents, Non-Steroidal - blood; Anti-Inflammatory Agents, Non-Steroidal - pharmacokinetics; Blood; Body Weight; Chronic Disease; COXIB; Diphenylamine; Diphenylamine - analogs & derivatives; Diphenylamine - blood; Diphenylamine - pharmacokinetics; Dog; Dog Diseases; Dog Diseases - blood; Dog Diseases - drug therapy; Dogs; drug therapy; Female; hematologic tests; kidneys; liver; Male; osteoarthritis; Osteoarthritis - blood; Osteoarthritis - drug therapy; Osteoarthritis - veterinary; patients; pharmacokinetics; Phenylacetates; Phenylacetates - blood; Phenylacetates - pharmacokinetics; population characteristics; Population pharmacokinetics; Robenacoxib; Sex Factors; veterinary; Veterinary medicine; France; Switzerland; LLOQ; Population pharmacokinetics; RSE; BLQ; NSAID; FOCE; EBEs; COX; AUC; Robenacoxib; COXIB; IOV; OA; IIV; Dog; OFV; osteoarthritis; inter-occasion variability; objective function value; non-steroidal anti-inflammatory drug; lower limit of quantification; cyclooxygenase; area under the curve; first order conditional estimation method; relative standard error; below limit of quantification; inter-individual variability; empiricial Bayes estimates
• DOI: 10.1016/j.rvsc.2013.04.021
• ISSN: 0034-5288; 1532-2661

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.