NCT02904434

Gastrointestinal Implications of Voriconazole Exposure

Gastrointestinal Implications of Voriconazole Exposure: Determining Age-dependent Differences in Intestinal Metabolism Affecting Oral Bioavailability of Voriconazole in Children

• Status: Withdrawn
• Phase: —
• Study type: Observational
• Enrollment: 0 (actual)
• Sponsor: Children's Hospital of Philadelphia · Academic / Other
• Sex: All
• Age: 2 Years – 17 Years
• Healthy volunteers: Not accepted

Summary

Voriconazole has better response rates, improved survival and less adverse side effects compared to other drugs for the treatment of invasive fungal infections making it a desirable therapeutic option for children. However, dosing is unpredictable in children and this leads to therapeutic failure. This study aims to understand the physiological differences between children and adults that leads to therapeutic failure of voriconazole in children.

Detailed description

Voriconazole clearance in children (2-12 years old) is 3-fold higher and bioavailability is one half of adult values. An important gap in knowledge exists that explain the mechanisms that result in higher clearance and lower bioavailability of voriconazole and places children at a substantial risk for sub-therapeutic concentrations and treatment failures. Preliminary data suggests that intestinal first-pass metabolism is responsible for the lower bioavailability in children, but not in adults. By inhibiting intestinal metabolism with grapefruit juice, the extent of the effect of intestinal first-pass metabolism on voriconazole pharmacokinetics can be determined. Inpatient children at the Children's Hospital of Philadelphia who are receiving oral voriconazole as standard of care will be enrolled in an open label, cross-over clinical trial to monitor plasma voriconazole levels after voriconazole administration with and without grapefruit juice to inhibit intestinal metabolism of voriconazole. The proposed research will elucidate the role of intestinal metabolism in the reduced oral bioavailability of voriconazole in children, which can be incorporated into a model simulation to guide accurate dosing.

Conditions

• Infection

Interventions

Type	Name	Description
OTHER	Grapefruit Juice	On day 1 of the study, subjects will receive their standard voriconazole dose with no grapefruit juice. On day 2 of the study, subjects will receive approximately 240mL of reconstituted grapefruit juice by mouth or via nasogastric tube 30 minutes prior to receiving a scheduled dose of voriconazole. Blood samples will be collected during the 12 hours following voriconazole dosing on both days of the study.

Timeline

• Start date: 2016-09-01
• Primary completion: 2020-06-01
• Completion: 2020-06-01
• First posted: 2016-09-19
• Last updated: 2020-04-09

Locations

1 site across 1 country: United States