Cystic Fibrosis
Conditions
Keywords
Cystic Fibrosis
Brief summary
The disposition of a number of drugs has been reported to be altered in patients with Cystic Fibrosis (CF). Changes in pharmacokinetic parameters observed included increased volumes of distribution and increased clearance of renally eliminated drugs. The purpose of this this study is to characterize the pharmacokinetics of IV lansoprazole and its metabolites in normal healthy children and children with Cystic Fibrosis (CF) ages 2 to \< 10 years. It is suspected that children with CF will have a more rapid clearance as compared to healthy children.
Detailed description
Cystic fibrosis (CF) impacts 1:2500 Caucasian newborns and results from a defect in the cystic fibrosis transmembrane conductance regulator chloride channel (CFTR) responsible for electrolyte regulation. Between 25 to 81% of the CF population have gastro-esophageal reflux disease (GERD), and proton pump inhibitors (PPIs) are frequently prescribed for this condition. Moreover, PPIs are commonly used in patients with CF to allow for better gastric acid stabilization so that pancreatic enzyme efficacy is optimized and nutritional status is improved. Lansoprazole is a PPI that is widely used for acid-related disorders including GERD. The disposition of a number of drugs has been reported to be altered in CF. Changes in pharmacokinetic parameters observed in patients with CF include increased volumes of distribution and increased clearance of renally eliminated drugs. To date, the pharmacokinetics of PPIs in patients with CF have not been characterized. This study is a pilot study to evaluate and compare the pharmacokinetics of a single dose of IV lansoprazole in CF and normal children 2 to \< 10 years of age. A goal of 12 evaluable subjects ranging from 2 to \< 10 years of age including both males and females with CF ∆F508 genotype will be recruited from CF clinic or inpatient. As a comparison group, six evaluable subjects who are normal, healthy children of similar demographic profile (age, gender, and race) will be recruited. After informed consent/assent is obtained, screening procedures will be completed within 30 days of study participation. The pre-study screen includes an age-appropriate physical exam, medical history (current medication/herbal use), vital signs (non-crying sitting blood pressure and heart rate), height, weight, AST, ALT, and CBC. Subjects will be studied during a current hospitalization or scheduled for an approximately 12-hour study visit.
Interventions
DRUGLansoprazole
Sponsors
Arkansas Children's Hospital Research Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 10 Years
Healthy volunteers
Yes
Inclusion criteria
* Subjects who have the diagnosis of CF with the ∆F508 genotype (hetero- or homozygous) or who are normal and healthy as determined by the principal investigator, have in the past year received a H2 receptor antagonist, PPI, or antacid, and do not meet any of the
Exclusion criteria
. * Subjects of either gender and all races and ethnicity age 2 to \< 10 years. * Written informed consent from parent or guardian who has sufficient intellectual capacity to understand the study and adhere to the procedures and as applicable (i.e., subjects ≥ 7 years of age), subject assent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Examine the PK enantiomers of IV lansoprazole and metabolites, in normal children and children with CF. | — |
Secondary
| Measure | Time frame |
|---|---|
| To compare the differences in the PK enantiomers of IV lansoprazole and metabolites, between children with CF and normal healthy children | — |
| Examine the PK enantiomers of IV lansoprazole and metabolites in relationship to CYP2C19 genotype in children with CF and normal healthy children | — |
| To assess the effects of ontogeny on IV lansoprazole drug disposition | — |
Countries
United States
Outcome results
None listed