To the Editor:
We appreciate the comments offered by Dr Friesen in response to our study examining the impact of age and CYP2C19 genotype on the pharmacokinetics of pantoprazole in pediatric patients who are obese.1 Dr Friesen is correct in that our study cohort did not include a group of children who were not obese. Consequently, any comparisons that we offered carried the caveat of having used a historical cohort for comparison.
As described in our study,1 our goal was to understand whether pantoprazole dosing in children and adolescents who are obese was best accomplished using an index of body size that was different than total body weight to achieve similar systemic drug exposures that had been reported previously for children who are not obese.2 We found that lean body weight (LBW) achieved this, as compared with children who are not obese dosed via total body weight. The extrapolation of LBW for historic children who are not obese, based on an absolute body mass index (BMI) of 20 kg/m2, as proposed by Friesen, raises some concern and highlights the problem with using absolute BMI values for comparisons across different pediatric ages (ie, 6–17 years, as in our study population1). For example, a BMI of 20 kg/m2 translates to >97th BMI percentile for age for a 6-year-old girl (obese), 85th percentile for an 11-year-old girl (overweight), and approximately 50th percentile for a 15-year-old girl (normal weight).3 Therefore, the LBW estimates calculated by Dr Friesen for historic peers who are normal weight are inaccurate, as a BMI of 20 kg/m2 is not always within the normal range, depending on the child’s age.
Our study provides evidence suggesting that, in addition to CYP2C19 genotype, age and obesity per se may influence pantoprazole disposition. This assertion remains to be explored using an approach that combines relevant genomics, metabolomics (eg, looking at specific metabolic pathways for pantoprazole), and pharmacokinetics performed in a prospective study that involves a cohort of children of normal weight and a cohort of children who are overweight/obese.
Contributor Information
Valentina Shakhnovich, Division of Gastroenterology, Hepatology and Nutrition, Division of Clinical Pharmacology, Toxicology and Therapeutic Innovation, The Children’s Mercy Hospital, Kansas City, Missouri.
Gregory L. Kearns, Department of Pediatrics, University of Arkansas for Medical Sciences, Section of Clinical Pharmacology and Toxicology, Arkansas Children’s Hospital, Little Rock, Arkansas.
References
- 1.Shakhnovich V, Smith PB, Guptill J, James L, Collier D, Wu H, et al. Obese children require lower doses of pantoprazole than non-obese peers to achieve equal systemic drug exposures. J Pediatr 2018;193:102–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Ward RM, Kearns GL, Tammara B, Bishop P, O’Gorman MA, James LP, et al. A multicenter, randomized, open-label, pharmacokinetics and safety study of pantoprazole tablets in children and adolescents aged 6 through 16 years with gastroesophageal reflux disease. J Clin Pharmacol 2011;51:876–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.World Health Organization. Growth reference data for 5–19 years. http://www.who.int/growthref/en/. Accessed February 19, 2018.