Pharmacokinetics of Meloxicam in Patients With Juvenile Rheumatoid Arthritis

Abstract

The pharmacokinetics of a meloxicam suspension were studied in 18 children with juvenile rheumatoid arthritis. Children received a single 0.25-mg/kg dose up to a maximum of 15 mg. Pharmacokinetic parameters after the first dose were calculated by noncompartmental methods. Geometric mean (percent coefficient of variation for geometric mean [gCV]) C(max), AUC(0- infinity ), apparent clearance, apparent volume of distribution, and elimination half-life values were 1.24 microg/mL (47% gCV), 25.6 microg x h/mL (81% gCV), 0.17 mL/min/kg (83% gCV), 0.19 L/kg (63% gCV), and 13.4 hours (54% gCV) in the younger group and 1.89 microg/mL (25% gCV), 35.8 microg x h/mL (21% gCV), 0.12 mL/min/kg (23% gCV), 0.13 L/kg (22% gCV), and 12.7 hours (21% gCV) for the older group, respectively. Area under the curve, volume of distribution, and clearance tended to be higher in the younger group, whereas elimination half-lives were similar. A post hoc comparison to pharmacokinetic data in adults revealed no relevant differences. Thus, a common body weight-normalized dose is considered appropriate for children older than 2 years.

Pharmacokinetics and Safety of Oral Administration of Meloxicam to Foals

“…The clearance of meloxicam after oral administration to foals was more rapid than has been reported for adult horses . Although clearance of NSAIDs is typically prolonged in foals/neonates, our findings are consistent with human pediatric studies, where the clearance of meloxicam was increased in juvenile patients . The metabolism and elimination of meloxicam by adult horses differs slightly from reports in other species, but in all species studied to date, the compound is metabolized by hepatic oxidation utilizing the cytochrome P450 2C subgroup to 4 principal, inactive metabolites, which are then excreted in urine and feces .…”

“…[8][9][10]14,19,20 Although clearance of NSAIDs is typically prolonged in foals/neonates, 3,4,21 our findings are consistent with human pediatric studies, where the clearance of meloxicam was increased in juvenile patients. 22 The metabolism and elimination of meloxicam by adult horses differs slightly from reports in other species, 23 but in all species studied to date, the compound is metabolized by hepatic oxidation utilizing the cytochrome P450 2C subgroup to 4 principal, inactive metabolites, which are then excreted in urine and feces. 24,25 As only very low levels of parent compound are present in urine, bile, or feces, meloxicam is evidently cleared almost exclusively by metabolism, and biotransformation governs elimination in all species studied to date.…”

Dosing Regimen Determination for Juvenile Idiopathic Arthritis: A Review of Studies During Drug Development11Opinions expressed in this manuscript are those of the authors’ and do not reflect the views or policies of the US Food and Drug Administration.

“…After body weight adjustment, the exposure was independent of age. This result was consistent with what Burgos‐Vargas et al37 had reported. Meloxicam oral suspension was shown to be bioequivalent to the adult tablet formulation during the adult development program.…”

Pharmacokinetics and safety of firocoxib after oral administration of repeated consecutive doses to neonatal foals

“…Potentially, the effect of ontogeny and maturation of drug-metabolizing pathways in the liver of neonatal animals could also account for a portion of the faster clearance. Raidal et al (2013) speculated that clearance of meloxicam in neonatal foals was increased due to the fact that the cytochrome P450 enzyme systems are among the most abundant liver enzymes, and therefore, younger animals have a relative abundance of these enzymes when liver volume is normalized to body weight, which increases drug clearance (Blanco et al, 2000;Burgos-Vargas et al, 2004). Additionally, the gastrointestinal tract, blood cells and potentially the lungs may be affecting the rate of firocoxib metabolism in this age group (Allegaert et al, 2007).…”