Obese Children Require Lower Doses of Pantoprazole Than Nonobese Peers to Achieve Equal Systemic Drug Exposures.

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.

Predictors of outcome after acetaminophen poisoning in children and adolescents.

OBJECTIVE: Shortened courses of N-acetylcysteine may be acceptable in patients with acetaminophen poisoning who are at low risk for toxicity. The goal of this study was to determine which clinical findings best identified patients at lowest risk for acetaminophen-related hepatotoxicity after an acute overdose. STUDY DESIGN: This was a retrospective analysis, throughout 10 years, of hospital admissions for acute acetaminophen poisoning, with inclusion criteria being an acetaminophen concentration above the possible toxicity line by nomogram, arrival within 24 hours, and an initial prothrombin time (PT), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) measured within 24 hours of ingestion. Clinical parameters capable of identifying patients most and least likely to have hepatotoxicity were evaluated by using sensitivity and specificity testing. RESULTS: Of 95 patient charts identified, 41 met all inclusion criteria, with 16 patients having hepatotoxicity. PT, AST, and ALT within the first 24 hours postingestion did not identify all patients who had hepatotoxicity. The best predictor of a low risk of toxicity was the presence of normal values for the PT, AST, or ALT within 48 hours of ingestion. CONCLUSIONS: These data suggest that all patients with an acute acetaminophen overdose should be observed and treated for at least 48 hours postingestion.