Authors: Zhang, Weijiang; Kukulka, Michael; Witt, Galen; Sutkowski-Markmann, Debra; North, Janine; Atkinson, Stuart

Source: Pediatric Drugs, Volume 10, Number 4, 2008 , pp. 265-274(10)

Publisher: Adis International

Abstract:

Background: Evidence suggests that age may affect the pharmacokinetics of lansoprazole in pediatric patients, but little information is available in neonates and infants.

Objective: To determine the pharmacokinetics of lansoprazole in neonates and infants <1 year of age with gastroesophageal reflux disease (GERD)-associated symptoms.

Methods: Two single- and repeated-dose, randomized, open-label, multicenter studies were conducted. Studies involved a pretreatment period of 7 or 14 days, a dose administration period of 5 days, and a follow-up period of 30 days for adverse events collection. The studies were conducted in both hospital and private clinic settings. The studies were performed in 24 neonates (aged ≤28 days) and 24 infants (aged >28 days, but <1 year) with GERD-associated symptoms diagnosed by medical history and the clinical judgment of the treating physician. Participants received lansoprazole 0.5 or 1.0 mg/kg/day (neonates) or 1.0 or 2.0 mg/kg/day (infants) for 5 days. Plasma pharmacokinetic parameters on dose administration day 1 were calculated, and plasma concentrations on day 5 were obtained.

Results: The pharmacokinetics of lansoprazole were approximately dose proportional. After a single dose in neonates, the mean maximum plasma concentrations (C_max) were 831 and 1672 ng/mL, and the mean area under the plasma concentration-time curve (AUC) values were 5086 and 9372 ng · h/mL for lansoprazole doses of 0.5 and 1.0 mg/kg, respectively. The time to C_max (t_max) [3.1 hours] and harmonic mean terminal elimination half-life (t_½) [2.8 hours] were slightly longer in neonates receiving 0.5 mg/kg than the t_max (2.6 hours) and t_½ (2.0 hours) values observed in neonates receiving 1.0 mg/kg. Mean oral clearance (CL/F) was identical for the two doses (0.16 L/h/kg). After a single 1.0 or 2.0 mg/kg dose in infants, the lansoprazole C_max values were 959 and 2087 ng/mL and the mean AUC values were approximately 2203 and 5794 ng · h/mL, respectively. The mean t_max and mean t_½ were 1.8 hours and 0.8 hours, respectively, for both doses (1.0 or 2.0 mg/kg), while mean CL/F was 0.71 and 0.61 L/h/kg, respectively. In both patient groups, mean plasma concentrations on day 5 were similar to day 1 concentrations. No clinically meaningful accumulation was observed following 5 days' dose administration. Plots of lansoprazole pharmacokinetics against chronologic age showed that dose-normalized C_max, t_½, and AUC were two, three, and five times higher, respectively, in study participants aged ≤10 weeks than in study participants aged >10 weeks-1 year. Lansoprazole was well tolerated in all patients.

Conclusions: The pharmacokinetics of lansoprazole in pediatric patients are age dependent, with those aged ≤10 weeks showing higher plasma exposure and lower plasma clearance than those aged >10 weeks-1 year. Thus, pediatric patients aged ≤10 weeks require a lower dose of lansoprazole than pediatric patients aged >10 weeks to achieve similar plasma exposure.

Keywords: Infants; Lansoprazole; Neonates

Document Type: Research article

Affiliations: 1: TAP Pharmaceutical Products Inc., Lake Forest, Illinois, USA

Publication date: 2008-01-01

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• In this Subject: Pediatrics ,  Pharmacology
• By this author: Zhang, Weijiang ;  Kukulka, Michael ;  Witt, Galen ;  Sutkowski-Markmann, Debra ;  North, Janine ;  Atkinson, Stuart

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