Pharmacokinetic Evaluation of Nontuberculous Mycobacterial Antibiotics in Cystic Fibrosis Versus Controls

Date de début de l'étude : 1 octobre 2014

CF Subject Inclusion Criteria: * CF diagnosis defined as a sweat chloride \>60mEq/L and/or the presence of two disease-causing CFTR mutations. * Ages 16 years and above. * Pancreatic insufficient status defined as previous fecal pancreatic elastase \<100mcg/g stool and/or having 2 disease-causing CFTR mutations known to be associated with pancreatic insufficiency, and taking supplemental pancreatic enzymes between 1000-2500 lipase units/kg/meal. * No positive NTM cultures in the last 2 years. * Pulmonary function: Most recent FEV1 \> 40% predicted. * Willing to participate in and comply with the study procedures, and willingness of a parent or legally authorized representative to provide written informed consent for those subjects less than 18 years of age. Healthy Control Inclusion Criteria: * Ages 18 years and above. * BMI below 30 to best match CF body type. * Willing to participate in and comply with the study procedures, and willingness of a parent or legally authorized representative to provide written informed consent for those subjects less than 18 years of age. CF Subject Exclusion Criteria: * Allergy or intolerance to rifampin, ethambutol, or azithromycin. * Hepatic insufficiency defined as having an AST or ALT greater than three times the upper limit of normal at the screening appointment. * Previous surgical bowel resection. * Previous lung transplant. * Use of medications known to interact with the antimycobacterial drug levels; of note, the most common interactions in CF patients are the use of itraconazole, voriconazole, and ivacaftor. We will have subjects hold H2 blockers and proton pump inhibitors for 3 days prior to each PK study day. * Inability to hold azithromycin: Subjects will not be excluded if they are on chronic azithromycin for immunomodulatory purposes; however, we will ask that the subjects hold the azithromycin starting at the screening visit, through a 2 week wash-out period prior to Visit 2, and remain off through the end of Visit 3 (about 4 weeks total). * Acute exacerbations: exclusion if any addition of oral, IV, or inhaled antibiotics, or an acute gastrointestinal illness with vomiting or diarrhea in the 2 weeks prior to each visit. No exclusion for previously prescribed alternating chronic inhaled or oral antibiotics. * We will also exclude pregnant women (urine pregnancy test will be performed for females on the day of each PK study) and decisionally challenged subjects. Healthy Control Exclusion Criteria: * Allergy or intolerance to rifampin, ethambutol, or azithromycin. * Hepatic insufficiency defined as having an AST or ALT greater than three times the upper limit of normal at the screening appointment. * Previous chronic GI disease or surgical bowel resection. * Use of medications known to interact with the antimycobacterial drug levels. We will have subjects hold H2 blockers and proton pump inhibitors for 3 days prior to the PK study day. * Acute illness: exclusion if respiratory illness requiring antibiotics or gastrointestinal illness with vomiting or diarrhea in the 2 weeks prior to the PK visit. * We will also exclude pregnant women (urine pregnancy test will be performed on the day of PK study) and decisionally challenged subjects.