Pharmacokinetics of a novel 5-lipoxygenase inhibitor (ABT-761) in pediatric patients with asthma.

Abstract

OBJECTIVE:

The pharmacokinetics of an N-hydroxyurea analog, ABT-761 in asthmatic pediatric patients with asthma were investigated.

METHODS:

A total of 24 patients were enrolled into this 8-day single- and multiple-dose study. Patients received daily doses of ABT-761 according to their body weight: patients of 20-38 kg received 50 mg; patients >38 kg but < or = 55 kg received 100 mg, and patients >55 kg received 150 mg.

RESULTS:

The mean values for the terminal phase t1/2 were 16-17 h after multiple-dose administration. When normalized for body weight, the mean day 8 Cl(f) values for 50-, 100-mg, and 150-mg doses were 0.57 (n=13), 0.51 (n=10), and 0.43 (n=1) ml x min(-1) x kg(-1), respectively, while the mean Vz/f values ranged from 0.75 to 0.77 l x kg(-1). The mean accumulation ratio observed (day 8 to day 1 AUC0-24 ratio) of ABT-761 was approximately 1.7, which is consistent with the t1/2 of this drug. Body weight, age, and body surface area were virtually identical in explaining the variability in dose-normalized Cmax and AUC values (R2=0.61-0.68). The percents of variance explained by these three variables were within a range of 3% for each pharmacokinetic parameter.

CONCLUSIONS:

The pharmacokinetics of ABT-761 in children were similar to those previously reported in adults. Body weight, age, or body surface area can be used to provide dosing adjustment for ABT-761 in pediatric patients.

• Authors: S L Wong, G L Kearns, J P Kemp, J Drajesk, M Chang, C S Locke, L M Dube, W M Awni
• Journal: European journal of clinical pharmacology (Eur J Clin Pharmacol) 1998 Nov-Dec Vol. 54 Issue 9-10 Pg. 715-9 ISSN: 0031-6970 [Print] Germany
• PMID: 9923573 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• Lipoxygenase Inhibitors
• atreleuton
• Hydroxyurea

Topics

• Adolescent
• Area Under Curve
• Asthma (metabolism)
• Body Surface Area
• Body Weight (physiology)
• Child
• Chromatography, High Pressure Liquid
• Female
• Half-Life
• Humans
• Hydroxyurea (analogs & derivatives, pharmacokinetics)
• Lipoxygenase Inhibitors (pharmacokinetics)
• Male