Pharmacokinetics of Pantoprazole and CYP2C19 Activity in Children and Adolescents With GERD: A Pilot Study
Status:
Completed
Trial end date:
2015-10-01
Target enrollment:
Participant gender:
Summary
The World Health Organization has declared childhood obesity to be "one of the most serious
public health challenges of the 21st century,"
(http://www.who.int/dietphysicalactivity/childhood). Given that obese children are generally
excluded from clinical trials, little to no information exists regarding the impact of
obesity on drug disposition and drug action, creating a gap in physicians' knowledge on how
to appropriately select the dose of many critical medications (e.g., anticancer agents), so
as to prevent toxicity associated with overdosing, while avoiding the harms of
under-treatment. The proposed study will examine the effect of obesity on the metabolism of a
commonly used medication, the proton pump inhibitor pantoprazole, by exploring the
relationships between age, obesity, basal metabolic rate and genetic control of the enzyme
primarily responsible for pantoprazole metabolism. We will also validate a simple breath test
that can be used to predict pantoprazole dose requirement for obese children.
The study is designed to test the following experimental hypotheses:[13C]-pantoprazole
pharmacokinetic parameters are not different between non-obese and obese children and
adolescents, collectively (both age groups combined) or stratified by age group (SA 1)
[13C]-pantoprazole pharmacokinetic parameters or DOB values (and thus, CYP2C19 activity) are
not different between males and females (SA 1 & 2) [13C]-pantoprazole pharmacokinetic
parameters and DOB (Delta over baseline) values (and thus, CYP2C19 activity) are independent
of age over the age range of 6 to 17 years (SA 1 & 2) Obesity does not alter the relative
contributions of CYP2C19-dependent and non-CYP2C19-dependent (i.e., CYP3A4) metabolism of
pantoprazole, as measured by the urinary ratio of 4-hydroxy-pantoprazole to pantoprazole
sulfone (SA 1 & 2) The [13C]-pantoprazole breath test, by determining DOB at discrete time
point(s), is a non-invasive measure of CYP2C19 phenotype (SA 2) Clearance of pantoprazole
(surrogate for CYP2C19 activity) is a function of REE in obese and non-obese children and
adolescents (SA 3) Pantoprazole clearance (surrogate for CYP2C19 activity) is associated with
fat distribution, as determined by waist-to-hip ratios (SA 3)