Age-related changes in the pharmacokinetics of meloxicam after intravenous administration in sheep

Abstract

The pharmacokinetics of meloxicam was studied in 1-, 6-, and 12-month- old sheep following a single intravenous (i.v.) dose of 1 mg/kg. The experiments were carried out when the Romanov sheep were 1 month old (7.93 +/- 0.91 kg), 6 months old (27.47 +/- 4.91 kg), and 12 months old (37.10 +/- 3.64 kg). Meloxicam concentration in plasma was determined by high-performance liquid chromatography and the data collected were evaluated by non-compartmental kinetic analysis. Meloxicam was detected in the plasma up to 72 h following i.v. administration in all age groups. The volume of distribution at steady state (Vdss) and total body clearance (ClT) were significantly higher in 1- month- old (304.87 mL/kg and 16.57 mL/h/kg) than in 12- month- old (193.43 mL/kg and 10.50 mL/h/kg) sheep. The area under the concentration- time curve from 0 to 72 h value of meloxicam was lower in 1- month- old (58.51 h*mu g/mL) compared to 12- month- old (92.59 h*mu g/mL) sheep. There was no difference in t1/ 2.z value in different age groups. The body extraction ratio values for meloxicam ranged from 0.0186 to 0.0719 after i.v. administration in all age groups. Meloxicam showed an increase in plasma concentration and a decrease in Vdss and ClT in 12- month- old compared to 1- month- old sheep. Compared to 1- month- old and 12- month- old sheep, there was no difference in these parameters in 6- month- old sheep. Because the age of sheep has an influence on the pharmacokinetics of meloxicam, dosage apparently may need to be adjusted for age.