Pharmacokinetics of IV Pantoprazole in Pediatric Patients

Ferron, Géraldine M.; Schexnayder, Stephen M.; Marshall, James D.; Blumer, Jeffrey L.; Rodarte, Alexander; Abell, Madelyn; Mako, Barbara; Fraga, Polly; Getsy, John; Paul, Jeff

doi:10.1016/s0009-9236(03)90491-7

Cited by 8 publications

(9 citation statements)

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“…To date, studies of PPIs conducted in pediatric populations have not been able to demonstrate a statistically significant correlation between age and PK parameters. [6][7][8][9][10]34 A similar conclusion was obtained from the current data when the PK parameters for pantoprazole (including λz, which is not influenced by absorption) from CYP2C19 extensive metabolizers were examined in association with age. The apparent age-independence of pantoprazole PK is further illustrated by similarity in pantoprazole plasma CL after IV administration in children ranging in age from 2 to 16 years and data generated from healthy adults (data on file, Byk-Gulden (Altanta) Protocol No.…”

Section: Discussionsupporting

confidence: 85%

“…In contrast to pantoprazole, the PK of omeprazole and lansoprazole have been well characterized in children older than 2 years of age with acid‐related diseases. Available PK data for omeprazole, 8 pantoprazole, 9 and lansoprazole 10 suggest a similarity between adult and pediatric data that supports the use of exposure‐response correlates established for adults to guide the dosing of PPIs in pediatric patients requiring acid‐suppression therapy 6 …”

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confidence: 85%

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

Kearns

Blumer

Schexnayder

et al. 2008

The Journal of Clinical Pharma

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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.

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Section: Discussionsupporting

confidence: 85%

mentioning

confidence: 85%

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

Kearns

Blumer

Schexnayder

et al. 2008

The Journal of Clinical Pharma

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“…One included 14 paediatric intensive care patients between 2 and 16 years of age receiving i.v. pantoprazole [22]. The only kinetic parameter reported in the study was the mean t 1/2 , which was shorter than the median t 1/2 observed in our patients (1.1 ± 0.5 h compared with 2.0 h (0.7–11.8 h)).…”

Section: Discussioncontrasting

confidence: 74%

“…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%

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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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