Single‐Dose Pharmacokinetics of Oral and Intravenous Pantoprazole in Children and Adolescents

Abstract

The primary objective was to determine the pharmacokinetics of single oral and intravenous doses of pantoprazole in children 2 to 16 years of age. The secondary objective was to assess the safety and tolerability of these doses. Male and female hospitalized and nonhospitalized patients from ages 5 to 16 years received single oral doses (20 mg or 40 mg), and those from ages 2 to 16 years received single intravenous doses (0.8 mg/kg or 1.6 mg/kg) of pantoprazole. The plasma concentration-time data for each patient were analyzed using noncompartmental methods. Routine safety and tolerability assessments were also obtained. The mean values for peak plasma concentration and total area under the plasma concentration-time curve increased with increasing dose. Pharmacokinetic values were similar in patients from ages 2 to 16 years and to those previously obtained in adults. Statistically significant differences were observed for dose-normalized pantoprazole area under the plasma concentration-time curve when compared between CYP2C19 extensive metabolizers with 1 versus 2 functional alleles. All adverse events were mild in severity and considered to be unrelated to study drug. The pharmacokinetic profile of oral and intravenous pantoprazole was similar in children ages 2 to 16 years. The doses used here were safe and well tolerated in this population.

Impact of the CYP2C19*17 Allele on the Pharmacokinetics of Omeprazole and Pantoprazole in Children: Evidence for a Differential Effect

“…The current investigation was enabled by a reassessment of data and samples available from previous pharmacokinetic studies of omeprazole (Kearns et al, 2003b) and pantoprazole (Kearns et al, 2008) conducted in pediatric populations for the purpose of product labeling. The Institutional Review Boards at participating institutions approved both investigations, and subjects were enrolled by parental permission and patient assent, as appropriate.…”

“…The approvals contained provisions for data reanalysis and expanded genotype analysis of stored DNA specimens. Study designs, complete methods, and results were previously described in detail (Kearns et al, 2003b(Kearns et al, , 2008, and therefore only pertinent information is recapitulated in this brief communication.…”

“…The pantoprazole study (Kearns et al, 2008) reported two cohorts of children, an oral and an intravenous study arm. The orally dosed cohort consisted of 24 subjects (16 male) aged 10.8 Ϯ 3.4 years (range, 5-16 years) and weighing 45.0 Ϯ 19.9 kg (range, 20 -90 kg).…”

“…The approvals contained provisions for data reanalysis and expanded genotype analysis of stored DNA specimens. Study designs, complete methods, and results were previously described in detail (Kearns et al, 2003b(Kearns et al, , 2008, and therefore only pertinent information is recapitulated in this brief communication.The omeprazole study comprised 37 subjects, 23 of whom yielded evaluable pharmacokinetic data (Kearns et al, 2003b); these subjects were further investigated for CYP2C19*17. Ten or 20 mg of omeprazole was administered as a single solid oral dose to subjects aged 9.5 Ϯ 3.8 years (mean Ϯ S.D.…”

“…Ten or 20 mg of omeprazole was administered as a single solid oral dose to subjects aged 9.5 Ϯ 3.8 years (mean Ϯ S.D. ; range, 2-16 years) and weighing 26.2 Ϯ 15.1 kg (range, 11-75 kg), and 10 participants were male.The pantoprazole study (Kearns et al, 2008) reported two cohorts of children, an oral and an intravenous study arm. The orally dosed cohort consisted of 24 subjects (16 male) aged 10.8 Ϯ 3.4 years (range, 5-16 years) and weighing 45.0 Ϯ 19.9 kg (range, 20 -90 kg).…”