Cyclosporine A pharmacokinetics in a cardiac allograft recipient with a jejuno-ileal bypass.
A 41-year-old man with a 13-year history of JI bypass for morbid obesity developed idiopathic cardiomyopathy. A pretransplant CsA pharmacokinetic profile demonstrated inadequate PO absorption with no appreciable enterohepatic recirculation. Inadequate levels occurred after three hours and became undetectable after 18 hours. The patient's status did not permit JI bypass reversal before transplantation. IV CsA was administered before cardiac transplantation, and a continuous IV CsA infusion was maintained for 72 days through episodes of CMV reactivation infection and complications common to the immunosuppressed patient. JI bypass reversal was subsequently performed and IV CsA converted to oral form as intestinal function improved. A repeat PO CsA pharmacokinetic profile demonstrated a threefold rise in peak concentration, delayed smaller peak concentrations representing enterohepatic recirculation, and a steady-state blood level that persisted for 23 hours. We have found that pretransplant CsA pharmacokinetic analysis predicts CsA bioavailability and serves as a guide for achieving optimal CsA serum concentrations; adequate PO absorption and enterohepatic recirculation of CsA depends on the anatomical and functional integrity of the jejunum and ileum; continuous IV CsA infusion can be precisely adjusted for optimal therapeutic efficiency; and long-term CsA infusion can benefit critically ill transplant patients without increased morbidity.
Knight
G C
GC
Division of Surgery, Texas Heart Institute, Houston 77225.
Macris
M P
MP
Peric
M
M
Duncan
J M
JM
Frazier
O H
OH
Cooley
D A
DA
D000328:Adult; D003524:Cyclosporins / Q000493:pharmacokinetics*; D016027:Heart Transplantation; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods; D007581:Jejunoileal Bypass; D008297:Male
D003524:Cyclosporins