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Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures.
Shakhnovich, Valentina; Smith, P Brian; Guptill, Jeffrey T; James, Laura P; Collier, David N; Wu, Huali; Livingston, Chad E; Zhao, Jian; Kearns, Gregory L.
Afiliación
  • Shakhnovich V; Divisions of Gastroenterology & Clinical Pharmacology, Toxicology and Therapeutic Innovation, The Children's Mercy Hospital, Kansas City, MO. Electronic address: vshakhnovich@cmh.edu.
  • Smith PB; Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Duke Clinical Research Institute, Durham, NC.
  • Guptill JT; Department of Neurology, Division of Neuromuscular Medicine, Duke Clinical Research Institute, Durham, NC.
  • James LP; Department of Pediatrics, University of Arkansas for Medical Sciences Section of Clinical Pharmacology and Toxicology, Arkansas Children's Hospital, Little Rock, AR.
  • Collier DN; Department of Pediatrics and Center for Health Disparities, Division of General Pediatrics, East Carolina University, Greenville, NC.
  • Wu H; Department of Pediatrics, Division of Neonatal-Perinatal Medicine, Duke Clinical Research Institute, Durham, NC.
  • Livingston CE; Clinical Operations, Pediatric Trials Network.
  • Zhao J; The Emmes Statistical Group, Rockville, MD.
  • Kearns GL; Department of Pediatrics, University of Arkansas for Medical Sciences Section of Clinical Pharmacology and Toxicology, Arkansas Children's Hospital, Little Rock, AR.
J Pediatr ; 193: 102-108.e1, 2018 02.
Article en En | MEDLINE | ID: mdl-29389444
OBJECTIVE: To assess appropriate pantoprazole dosing for obese children, we conducted a prospective pharmacokinetics (PK) investigation of pantoprazole in obese children, a patient population that is traditionally excluded from clinical trials. STUDY DESIGN: A total of 41 obese children (6-17 years of age), genotyped for CYP2C19 variants *2, *3, *4, and *17, received a single oral dose of pantoprazole, ~1.2 mg/kg lean body weight (LBW), with LBW calculated via a validated formula. Ten post-dose pantoprazole plasma concentrations were measured, and PK variables generated via noncompartmental methods (WinNonlin). Linear and nonlinear regression analyses and analyses of variance were used to explore obesity, age, and CYP2C19 genotype contribution to pantoprazole PK. PK variables of interest were compared with historic nonobese peers treated with pantoprazole. RESULTS: Independent of genotype, when normalized to dose per kg total body weight, pantoprazole apparent clearance and apparent volume of distribution were significantly lower (P < .05) and systemic exposure significantly higher (P < .01) in obese vs nonobese children. When normalized per kg LBW, these differences were not evident in children ≥12 years of age and markedly reduced in children <12 years of age. CONCLUSIONS: LBW dosing of pantoprazole led to pantoprazole PK similar to nonobese peers. Additional factors, other than body size (eg, age-related changes in CYP2C19 activity), appear to affect pantoprazole PK in children <12 years of age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02186652.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Reflujo Gastroesofágico / Inhibidores de la Bomba de Protones / Obesidad Infantil / Pantoprazol Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Child / Female / Humans / Male Idioma: En Revista: J Pediatr Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Reflujo Gastroesofágico / Inhibidores de la Bomba de Protones / Obesidad Infantil / Pantoprazol Tipo de estudio: Clinical_trials / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Child / Female / Humans / Male Idioma: En Revista: J Pediatr Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos