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

Abstract

OBJECTIVE:

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.

ANIMALS:

6 adult horses.

PROCEDURE:

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.

RESULTS:

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.

CONCLUSIONS AND CLINICAL RELEVANCE:

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.

• Authors: Pierre-Louis Toutain, Corinne C Cester
• Journal: American journal of veterinary research (Am J Vet Res) Vol. 65 Issue 11 Pg. 1533-41 (Nov 2004) ISSN: 0002-9645 [Print] United States
• PMID: 15566092 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Thiazines
• Thiazoles
• Meloxicam

Topics

• Animals
• Arthritis, Experimental (drug therapy, veterinary)
• Biomechanical Phenomena
• Chromatography, High Pressure Liquid
• Dose-Response Relationship, Drug
• Endpoint Determination (veterinary)
• Horse Diseases (metabolism)
• Horses
• Lameness, Animal (metabolism)
• Meloxicam
• Models, Biological
• Thiazines (blood, pharmacokinetics, therapeutic use)
• Thiazoles (blood, pharmacokinetics, therapeutic use)