Pharmacokinetics of etodolac in patients with stable juvenile rheumatoid arthritis

doi:10.1016/S0149-2918(99)80050-2

Clinical Therapeutics

Volume 21, Issue 10, October 1999, Pages 1715-1724

https://doi.org/10.1016/S0149-2918(99)80050-2 Get rights and content

Abstract

This was a single-center, open-label, single-dose pharmacokinetic study of etodolac in pediatric and adolescent patients with stable juvenile rheumatoid arthritis (JRA). Eleven male and female patients with JRA (8.1 to 14.8 years of age, weighing 26.4 to 59.5 kg) received a single oral dose of etodolac (200, 300, or 400 mg based on body weight). Clinical laboratory measurements, measurement of vital signs, and physical examinations were performed to monitor safety. Concentrations of etodolac were determined in plasma using high-performance liquid chromatography with ultraviolet detection with a limit of quantitation of 0.2 mg/L and were analyzed using a noncompartmental pharmacokinetic method. Pharmacokinetic parameters observed were consistent in magnitude and degree of variability with data from healthy adult subjects receiving a single 400- or 600-mg dose of etodolac. Although the mean fraction of unbound drug in patients with JRA was higher than in healthy adults, the oral clearance was independent of age. No serious adverse events occurred during this study. Etodolac yielded consistent pharmacokinetic values among stratified dose subgroups. Single doses of all etodolac treatments were well tolerated in both pediatric and adolescent patients.

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Recently, we have reported an IL based ME comprising 1-butyl-3-methylimidazolium bromide (BMIMBr) as IL and isopropyl myristate (IPM) stabilized by Tween 80 and Span 20 for dermal delivery of 5-fluorouracil, a poorly water soluble anticancer drug (Goindi et al., 2014). Etodolac (ETO) is a poorly water soluble NSAID used to relieve inflammation, swelling, stiffness, and pain associated with rheumatoid arthritis, osteoarthritis (Simon et al., 2004) and juvenile rheumatoid arthritis (Boni et al., 1999). It shows poor oral bioavailability, gastrointestinal and cardiovascular side effects following oral administration (Barakat, 2006).
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The population analysis based on the PK data from this study showed that the body weight was a significant covariate of clearance. The PK of etodolac was also reported in an open-label study, where a single body weight-based dose of etodolac (200–400 mg) was given to 11 JIA patients (8–14 years of age).38 PK parameters in pediatrics were consistent in magnitude and degree of variability with those from healthy adult subjects.
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Pharmacokinetics of etodolac in patients with stable juvenile rheumatoid arthritis

Abstract

Int J Pharm

J Pediatr

J Pediatr

The metabolic disposition of etodolac in rats, dogs, and man

Drug Metab Rev

Disposition and biotransformation of 14CC-etodolac in man

Xenobiotica

Treatment of juvenile rheumatoid arthritis with diclofenac sodium

Scand J Rheumatol

Pharmacokinetics of pirprofen in children with juvenile chronic arthritis

Eur J Drug Metab Pharmacokinet

Phannacokinetics of oral and rectal flurbiprofen in children

Eur J Clin Pharmacol

Disposition and biotransformation of ¹⁴CC-etodolac in man