Tacrolimus has been increasingly used in liver transplant patients to prevent rejection. The drug has relatively a narrow therapeutic window. We report here the changes in the kinetic profile following oral dose of tacrolimus, before and after reversal of Jejuno-ileal (J-I) bypass. Case 1: 57 year old lady underwent deceased liver transplantation (LTx) in February, 2003 for end stage liver disease related to (J-I) bypass, 20 years prior to LTx for obesity. Her stable dose of tacrolimus was 7mg twice a day, with trough concentration ranging from 5.2 to 6.4 ng/ml. She underwent reversal of (J-I) bypass seven months post LTx. Kinetic studies were performed prior to reversal of (J-I) bypass and 3 months after reversal with the stable oral dose of tacrolimus in steady state.
Immediately after reversal of (J-I) bypass her trough level increased to 25.4 ng/ml from 6.2 ng/ml. Tacrolimus was put on hold for 2 days and then restarted at 3mg twice a day. Subsequently she stabilized to 5 mg twice a day to achieve trough concentration ranging from 4.1 to 6.6 ng/ml. The area under the concentration curve (AUC) improved from 10.9 to 20.7 ng/ml/hr/mg, a two-fold increase with J-I reversal. Also peak value of twice the trough concentration was observed at three hours after the oral dose of tacrolimus, following reversal of I-J bypass, which was absent prior to reversal (figure below).
Prior to reversal of J-I Bypass patients required higher doses of tacrolimus and kinetic study did no show any peak value. After reversal of J-I bypass patient demonstrated regular peak value and required lower doses. Also AUC after J-I reversal improved by two fold. In the immediate postoperative period, toxic levels were observed probably because of large area of absorption with relative adynamic bowel activity. Careful monitoring is necessary in such situation to avoid tacrolimus related drug toxicity.