Pharmacokinetics of Mycophenolic Acid and Dose Optimization in Children After Intestinal Transplantation

Area of Science:

• Pharmacology
• Transplantation Medicine
• Pediatric Gastroenterology

Background:

• Mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (MPS) are crucial immunosuppressants in pediatric intestinal transplantation (Tx).
• Current dosing guidelines for MMF/MPS in pediatric intestinal transplant recipients are lacking.
• Achieving adequate mycophenolic acid (MPA) exposure is vital for graft survival.

Purpose of the Study:

• To determine the MMF/MPS dosage required to achieve a target MPA area under the plasma concentration-time curve (AUC0-12) of >30 mg·h·L in children post-intestinal Tx.
• To establish evidence-based dosing recommendations for MMF/MPS in this specific pediatric population.

Main Methods:

• A pharmacokinetic study was conducted in 8 pediatric intestinal transplant recipients (median age 9.4 years).
• Patients received either MMF or MPS, with initial doses monitored for MPA AUC0-12.
• Dosage adjustments were made to achieve the target MPA exposure.

Main Results:

• Initial median MMF starting dose was 687 mg·m⁻¹·day⁻¹.
• A significant proportion of patients (3/3 MPS, 2/6 MMF) had MPA AUC0-12 below the target of 30 mg·h·L.
• The median MMF dosage required an increase of 91% (to 1319 mg·m⁻¹·day⁻¹) to reach the target MPA AUC0-12.

Conclusions:

• An initial MMF dose of 600 mg/m² twice daily is recommended for pediatric intestinal transplant recipients on tacrolimus and steroids.
• This dose aims to achieve MPA exposure comparable to adults and children undergoing other organ transplants.
• Further research is needed to refine MPA dosing in pediatric intestinal transplant recipients.