Overview
This is a single center, open-label, prospective, investigation to quantify the effects liver congestion and fibrosis has on hepatic drug metabolism and transport in children, adolescents, and young adults with Fontan circulation.
Eligibility
Inclusion Criteria:
- > 8 years
- Status Post Fontan Completion
- Ability to provide informed permission-assent (<18 years) or consent (≥18 years)
- Fasting overnight (~8 hours)
Exclusion Criteria:
- Pregnancy
- Non-fasting
- Non-removable metal in body or where magnetic resonance imaging (MRI) is considered unsafe
- Sildenafil and/or Pravastatin therapy within last 2 months
- History of underlying or laboratory evidence of underlying intestinal, metabolic, autoimmune, renal disease that can alter Sildenafil and Pravastatin disposition (absorption, metabolism, distribution, or clearance)
- Pharmacotherapy that interacts with Sildenafil (cytochrome P450 3A4 and P450 3A5 (CYP3A4/5) inducers/inhibitors) and/or Pravastatin (organic anion transporting polypeptide (OATP1B1) inducers/inhibitors)
- Inability to swallow a tablet
- >5X the age-specific upper limit of normal for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total and conjugated bilirubin
- Diarrhea in the last 24 hours *History of solid organ transplantation