Pharmacokinetic-pharmacodynamic relationships and dose response to meloxicam in horses with induced arthritis in the right carpal joint

Abstract

To determine pharmacokinetic-pharmacodynamic (PK-PD) relationships and dose effects for meloxicam in horses and to propose a suitable dosage for use in clinical studies. 6 adult horses. The study was conducted by use of a randomized, Latin-square design. Arthritis was induced in the right carpal joint of each horse by administration of Freund's complete adjuvant. Various dosages of meloxicam (0, 0.25, 0.5, 1.0, and 2.0 mg/kg, IV) were then administered. Validated endpoints including stride length and overall clinical lameness score (scale of 0 to 20) were used to assess the effect of meloxicam. The dose-effect relationship was quantified by use of a maximum possible effect (Emax) model. For stride length (expressed as a relative percentage increase from control values), the median effective dose (ED50) was 0.120 mg/kg for an Emax of 11.15%. For clinical lameness score (expressed as an absolute increase from the control value), the ED50 was 0.265 mg/kg for an Emax of 9.16 units. The PK-PD analysis allowed calculation of a median effective concentration of 130 ng/mL for stride length and 195 ng/mL for lameness score. Use of the Emax model predicted a maximal possible increase in effect of 19.5% for stride length and 13.91 units for lameness score. For stride length and lameness score, the Hill coefficient (slope) was extremely high, which suggested a steep dose-effect relationship. Results of this study suggest that meloxicam is a potent anti-inflammatory drug in horses. A dosage of 0.6 mg/kg/d would be appropriate for use in a clinical study.