IMProving DRug Dosing and Outcomes for Single VEntricle Patients With Fontan Associated Liver Disease

IMProving DRug Dosing and Outcomes for Single VEntricle Patients With Fontan Associated Liver Disease

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.

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