Pantoprazole Disposition in Pediatrics

Kearns, Gregory L.; Ferron, Géraldine M.; James, Leonard P.; Jl, Blumer; Gaedigk, Andrea; Mayer, Philip; Abel, Manfred; Getsy, John; Leeder, J. Steven; Paul, Jeffrey

doi:10.1016/s0009-9236(03)90496-6

Cited by 7 publications

(12 citation statements)

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“…In contrast, for patients presenting one or many of these factors, predicted pantoprazole CL are lower than that reported by Kearns et al. [23]. A similar decrease in omeprazole CL attributed to slower metabolism had been previously found in critically ill paediatric transplant patients [31].…”

Section: Discussionsupporting

confidence: 56%

“…However, using the adult value for pantoprazole bioavailability ( F = 77%) [56], the mean systemic CL of the extensive metabolizers studied by Kearns et al. [23] would approximate 0.23 l h −1 kg −1 . This is similar to the pantoprazole CL predicted from our final POPPK model for patients aged 2–5 years without SIRS, hepatic dysfunction and not taking CYP2C19 inhibitors (Figure 3A).…”

Section: Discussionmentioning

confidence: 99%

“…To date, two paediatric trials have studied the pharmacokinetics of pantoprazole [22, 23]. One included 14 paediatric intensive care patients between 2 and 16 years of age receiving i.v.…”

Section: Discussionmentioning

confidence: 99%

“…The second study was performed in 24 noncritically ill paediatric patients, between 6 and 16 years old, who received pantoprazole orally and included 21 extensive and three poor CYP2C19 metabolizers [23]. Among the extensive metabolizers, the mean apparent CL (CL/ F ) was 0.30 l h −1 kg −1 .…”

Section: Discussionmentioning

confidence: 99%

“…To date, there are limited data regarding the pharmacokinetics of pantoprazole in children [22, 23], with essentially no data for infants <2 years old. Evaluation of i.v.…”

Section: Introductionmentioning

confidence: 99%

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Population pharmacokinetics of intravenous pantoprazole in paediatric intensive care patients

Pettersen¹,

Mouksassi²,

Théôret

et al. 2009

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The use of intravenous pantoprazole, a proton pump inhibitor, has been increasing in the paediatric intensive care unit.• Despite this increased use, data on the disposition of intravenous pantoprazole in paediatric intensive care patients are very scarce. WHAT THIS STUDY ADDS• Our population approach has determined the pharmacokinetic parameters of intravenous pantoprazole in paediatric intensive care patients and the relative importance of factors influencing its disposition.• Pantoprazole clearance was significantly influenced by developmental changes and by the presence of systemic inflammatory syndrome, hepatic dysfunction and CYP2C19 inhibitors. AIMSTo characterize the pharmacokinetics of intravenous pantoprazole in a paediatric intensive care population and to determine the influence of demographic factors, systemic inflammatory response syndrome (SIRS), hepatic dysfunction and concomitantly used CYP2C19 inducers and inhibitors on the drug's pharmacokinetics. METHODSA total of 156 pantoprazole concentration measurements from 20 patients (10 days to 16.4 years of age) at risk for or with upper gastrointestinal bleeding, who received pantoprazole doses ranging from 19.9 to 140.6 mg/1.73 m 2 /day, were analysed using a population pharmacokinetic approach (NONMEM program). RESULTSThe best structural model for pantoprazole was a two-compartment model with zero order infusion and first-order elimination. Body weight, SIRS, age, hepatic dysfunction and presence of CYP2C19 inhibitors were significant covariates affecting clearance (CL), accounting for 75% of interindividual variability. Only body weight significantly influenced central volume of distribution (Vc). In the final population model, the estimated CL and Vc were 5.28 l h -1 and 2.22 l, respectively, for a typical 5-year-old child weighing 20 kg. Pantoprazole CL increased with weight and age, whereas the presence of SIRS, CYP2C19 inhibitors and hepatic dysfunction, when present separately, significantly decreased pantoprazole CL by 62.3, 65.8 and 50.5%, respectively. For patients aged between 6 months and 5 years without SIRS, CYP2C19 inhibitor or hepatic dysfunction, the predicted pantoprazole CL is faster than that reported in adults. CONCLUSIONThese results provide important information for physicians regarding selection of a starting dose and dosing regimens of pantoprazole for paediatric intensive care patients based on factors frequently encountered in this population.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

“…To date, two paediatric trials have studied the pharmacokinetics of pantoprazole [22, 23]. One included 14 paediatric intensive care patients between 2 and 16 years of age receiving i.v.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…To date, there are limited data regarding the pharmacokinetics of pantoprazole in children [22, 23], with essentially no data for infants <2 years old. Evaluation of i.v.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Population pharmacokinetics of intravenous pantoprazole in paediatric intensive care patients

Pettersen¹,

Mouksassi²,

Théôret

et al. 2009

Brit J Clinical Pharma

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Proton Pump Inhibitors in Pediatrics: Relevant Pharmacokinetics and Pharmacodynamics

Kearns,

Winter

2003

J. pediatr. gastroenterol. nutr.

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A marked discordance between the disposition of proton pump inhibitors (PPIs) in plasma and the kinetics of effect suggests the need for new approaches to characterize the clinical pharmacology of PPIs in infants and children. An assessment of pharmacokinetics and pharmacodynamics must take into account the genetic polymorphism of CYP2C19 and the impact of ontogeny on the activity of this and other enzymes (e.g., CYP3A4) which affect the biotransformation of the PPIs and, thus, their plasma clearance. In addition, the potential effects of extemporaneous formulations of the drugs on their rate and extent of absorption must be considered. Because of the apparent safety of PPIs and a well‐demonstrated dose–response–effect relationship in adults, pediatric pharmacokinetic data and an exposure correlate, such as the dose–area‐under‐the‐plasma‐concentration‐versus‐time‐curve relationship, can be used as a bridge to determine pediatric dosing.

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Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD)

Ward

Tammara

Sullivan

et al. 2010

Eur J Clin Pharmacol

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Pantoprazole Disposition in Pediatrics

Abstract: Clinical Pharmacology & Therapeutics (2003) 73, P38–P38; doi:

Cited by 7 publications

References 0 publications

Population pharmacokinetics of intravenous pantoprazole in paediatric intensive care patients

Population pharmacokinetics of intravenous pantoprazole in paediatric intensive care patients

Proton Pump Inhibitors in Pediatrics: Relevant Pharmacokinetics and Pharmacodynamics

Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD)

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