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Age-Dependent Pharmacokinetics of Lansoprazole in Neonates and Infants

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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 (Cmax) 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 Cmax (tmax) [3.1 hours] and harmonic mean terminal elimination half-life (t1/2) [2.8 hours] were slightly longer in neonates receiving 0.5 mg/kg than the tmax (2.6 hours) and t1/2 (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 Cmax values were 959 and 2087 ng/mL and the mean AUC values were approximately 2203 and 5794 ng • h/mL, respectively. The mean tmax and mean t1/2 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 Cmax, t1/2, 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.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

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Acknowledgments

This analysis was funded in full by TAP Pharmaceutical Products Inc., Lake Forest, Illinois, USA (ClinicalTrials.gov identifiers: NCT00174928 and NCT00220818). Writing support was also funded by TAP Pharmaceutical Products Inc.

TAP Pharmaceutical Products Inc. was responsible for the study design; the collection, analysis and interpretation of data; and the decision to submit the paper for publication. Writing support was provided by Rx Communications (UK).

All authors of this paper were employees of TAP Pharmaceutical Products Inc. at the time the studies were conducted.

The authors would like to thank all investigators who participated in these studies. We also wish to thank the Clinical Research Organization (Kendle International Inc.) for coordinating this study, Kathleen Ruesch for her assistance in managing the study, and Rx Communications (UK) for its assistance in the preparation of this article. We would like to acknowledge the contribution of Darcy Mulford, TAP Pharmaceutical Products Inc., to the design and analysis of this study.

The authors would like to thank the six investigators for enrolling and caring for their patients. Special thanks to Professor W. Furgmaga-Jablonska (University Children’s Hospital, Lublin, Poland), Dr M. Springer (Louisiana State University Health Sciences, Shreveport, LA, USA), Professor M. Kaczmarski (Medical University of Bialystok, Bialystok, Poland), Professor K. Fyderek (Polish American Institute of Pediatrics, Krakow, Poland), and Dr I. Haddad (Private Practice, Youngstown, OH, USA).

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Authors and Affiliations

  1. TAP Pharmaceutical Products Inc., 675 North Field Drive, Lake Forest, Illinois, 60045, USA

    Weijiang Zhang,  Michael Kukulka, Galen Witt, Debra Sutkowski-Markmann, Janine North & Stuart Atkinson

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  1. Weijiang Zhang
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  2. Michael Kukulka
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Correspondence to Michael Kukulka.

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Zhang, W., Kukulka, M., Witt, G. et al. Age-Dependent Pharmacokinetics of Lansoprazole in Neonates and Infants. Pediatr-Drugs 10, 265–274 (2008). https://doi.org/10.2165/00148581-200810040-00005

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