Study of the Pharmacokinetics of Mycophenolate Mofetil in Patients Who Have Undergone Orthotopic Liver Transplantation

Study of the Pharmacokinetics of Mycophenolate Mofetil in Patients Who Have Undergone Orthotopic Liver Transplantation

OBJECTIVES: I. Determine the effects of bile externalization and antibiotic gut sterilization on the pharmacokinetics of mycophenolate mofetil in patients who have undergone orthotopic liver transplantation.

II. Correlate serum concentrations of mycophenolic acid with inosine monophosphate dehydrogenase activity in these patients.

PROTOCOL OUTLINE:

Patients begin a mycophenolate mofetil (MMF)-containing regimen within the first 5 days after transplantation. Patients have blood drawn on postoperative days 7, 21, 42, 70, 98, 126, and 154. Urine is collected on postoperative days 7, 21, and 42. Patients with T-tube bile externalization also have bile collected on postoperative day 7.

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Orthotopic liver or kidney transplant recipients who started on a mycophenolate mofetil-containing immunosuppressive regimen within 5 days after transplant

Kidney transplant recipients will serve as study controls

--Prior/Concurrent Therapy--

• No concurrent bile acid sequestrants
• No mycophenolate mofetil as part of rescue therapy regimen
• No concurrent albumin replacement therapy

--Patient Characteristics--

Renal: Urine output at least 500 mL/day OR Creatinine less than 2.5 mg/dL

Other:

• Not pregnant
• No mental incompetency
• No prisoners or parolees HIV negative
• No active infection defined as: Temperature above 101 F with WBC greater than 12,000/mm3 and left shift OR Two or more positive cultures of a single isolated organism from blood, urine, or sputum