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

The pharmacokinetic profile of pantoprazole granules was assessed in neonates and preterm infants with gastroesophageal reflux disease (GERD) in a multicenter, randomized, open-label trial. Patients were randomly assigned to either the pantoprazole 1.25 mg (approx. 0.6 mg/kg) or 2.5 mg (approx. 1.2-...

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Publicado en:European Journal of Clinical Pharmacology Vol. 66; no. 6; pp. 555 - 562
Autores principales: Ward R, Tammara B, Sullivan S, Stewart D, Rath N, Meng X, Maguire M, Comer G
Formato: clinical trial research Journal Article
Publicado: Springer Nature Jun2010
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jun2010
      vid: 66
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      pub: Springer Nature
      place: New York, New York
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        105203229
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        2010657527
        10.1007/s00228-010-0811-8
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        atl: Single-dose, multiple-dose, and population pharmacokinetics of pantoprazole in neonates and preterm infants with a clinical diagnosis of gastroesophageal reflux disease (GERD)
      aug:
        au:
          Ward R
          Tammara B
          Sullivan S
          Stewart D
          Rath N
          Meng X
          Maguire M
          Comer G
        affil: Pediatric Pharmacology Program, Department of Pediatrics, University of Utah, 417 Wakara, Suite 3510 Salt Lake 84108 USA
      sug:
        subj:
          Gastroesophageal Reflux Diagnosis
          Pantoprazole Sodium Pharmacodynamics
          Childbirth, Premature Evaluation
          Clinical Trials
          Demography
          Descriptive Statistics
          Funding Source
          Human
          Infant
          Infant, Newborn
          Pantoprazole Sodium Administration and Dosage
          Proton Pump Inhibitors Therapeutic Use
          Race Factors
          Safety
          Infant: 1-23 months
          Infant, Newborn: birth-1 month
      ab: The pharmacokinetic profile of pantoprazole granules was assessed in neonates and preterm infants with gastroesophageal reflux disease (GERD) in a multicenter, randomized, open-label trial. Patients were randomly assigned to either the pantoprazole 1.25 mg (approx. 0.6 mg/kg) or 2.5 mg (approx. 1.2-mg/kg) group and treated for >=5 consecutive days. Blood was sampled either at 0, 2, 8, and 18 h postdose or at 0, 1, 4, and 12 h postdose on day 1 and at 3 and 6 h postdose after >=5 consecutive doses. Cytochrome P450 2C19 (CYP2C19) and CYP3A4 genotypes were determined. Safety was monitored. Population pharmacokinetics (popPK) analyses were conducted using nonlinear mixed-effects modeling. The popPK modeling of the pantoprazole 1.25 mg and 2.5 mg groups obtained mean (±standard deviation) estimates for the area under the plasma concentration versus time curve (AUC) of 3.54 (±2.82) and 7.27 (±5.30) ug h/mL, respectively, and mean estimates for half-life of 3.1 (±1.5) and 2.7 (±1.1) h, respectively. Pantoprazole did not accumulate following multiple-dose administration. The two patients with the CYP2C19 poor metabolizer genotype had a substantially higher AUC than extensive metabolizers. No safety-related discontinuations occurred. In preterm infants and neonates, pantoprazole granules were generally well tolerated, mean exposures with pantoprazole 2.5 mg were slightly higher than that in adults who received 40 mg. While the half-life was longer, accumulation did not occur.
      pubtype: Academic Journal
      doctype:
        clinical trial
        research
        Journal Article
      ougenre: Article
    language: English
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