title: Conversion to neoral for neurotoxicity after primary adult liver transplantation under tacrolimus.
abstract: BACKGROUND
  Neurological complications after orthotopic liver transplantation (OLTX) have remained a major concern in a small proportion of patients. The etiology of these complications is often thought to be multifactorial: the influence of calcineurin inhibitors is occasionally thought to play an important role. When neurotoxicity occurs after OLTX under tacrolimus, it is usually a minor complication and responds readily to a reduction in the dosage of or a temporary withdrawal of tacrolimus. However, neurotoxic complications occasionally do not respond to this conventional process. Neoral is a microemulsion formulation of cyclosporine. It has more consistent pharmacokinetic parameters and improved bioavailability when compared with conventional cyclosporine. The aim of the present report was to evaluate the role of Neoral in OLTX recipients with neurotoxic complication who failed to respond to a reduction in the dosage of tacrolimus.
  
  
  METHODS
  Between August 1995 and November 1997, 330 adults (age >18 years) received primary OLTX under tacrolimus-based immunosuppression (mean age 52.6+/-11.4 years). There were 190 men and 140 women. Twenty-three (7%) patients (mean age 53.2+/-11.8 years; 17 men, 6 women) were converted to Neoral (mean 35+/-41 days after OLTX). These patients were followed until June 1998 (mean follow-up 22.7+/-7.8 months).
  
  
  RESULTS
  Four (17.4%) patients died during the follow-up period, and two patients underwent retransplantation. Neurological symptoms improved in all patients who survived. Adequate trough concentrations were achieved in all patients with p.o. Neoral. Nine (39%) patients experienced rejection episodes after conversion. Six (26.1%) patients were converted back to tacrolimus because of ongoing rejection (n=3), retransplantation (n=2), or persistent nausea and vomiting (n=1) without recurrence of the original neurological complication.
  
  
  CONCLUSIONS
  Neurological complications after OLTX disorders that occur under tacrolimus and that fail to respond to a reduction in the dosage can be treated safely by conversion to Neoral. However, the rate of rejection is up to 39%, and patients can often be converted back to tacrolimus without recurrence of the original neurological complication.
authors.affiliation: Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania 15213, USA.
authors.forename: A
authors.initials: A
authors.lastname: Jain
authors.forename: D
authors.initials: D
authors.lastname: Brody
authors.forename: I
authors.initials: I
authors.lastname: Hamad
authors.forename: N
authors.initials: N
authors.lastname: Rishi
authors.forename: E
authors.initials: E
authors.lastname: Kanal
authors.forename: J
authors.initials: J
authors.lastname: Fung
mesh_terms: D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000506:poisoning / Q000627:therapeutic use*; D016031:Liver Transplantation / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D011183:Postoperative Complications; D012086:Reoperation; D019233:Retreatment; D016559:Tacrolimus / Q000506:poisoning*; D014057:Tomography, X-Ray Computed
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus