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

Objective: The pharmacokinetics of an N-hydroxyurea analog, ABT-761 in asth matic pediatric patients with asthma were investigated. Methods: A total of 24 patients were enrolled into this 8-day single- and m ultiple-dose study. Patients received daily doses of ABT-761 according to t heir body weight: patients of 20-38 kg received 50 mg; patients >38 kg but less than or equal to 55 kg received 100 mg, and patients greater than or e qual to 55 kg received 150 mg. Results: The mean values for the terminal phase t(1/2) were 16-17 h after m ultiple-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.min(-1).kg(-1) respectively, while the mean V-2/f values ranged from 0.75 to 0.77 l.kg(-1). The mean accumulation ratio obse rved (day 8 to day 1 AUC(0-24) ratio) of ABT-761 was approximately 1.7, whi ch is consistent with the t(1/2) of this drug. Body weight, age, and body s urface area were virtually identical in explaining the variability in dose- normalized C-max and AUC values (R-2 = 0.61-0.68). The percents of variance explained by these three variables were within a range of 3% for each phar macokinetic parameter. Conclusions: The pharmacokinetics of ABT-761 in children were similar to th ose previously reported in adults. Body weight, age, or body surface area c an be used to provide dosing adjustment for ABT-761 in pediatric patients.