title: Tacrolimus-related adverse effects in liver transplant recipients: its association with trough concentrations.
abstract: BACKGROUND
  Tacrolimus is an important immunosuppressant administered to patients following liver transplantation (LT), with a recommended trough concentration of 8 to 11 ng/mL to prevent allograft rejection. We retrospectively examined our data to identify the tacrolimus trough concentration that combined efficacy with minimal adverse effects.
  
  
  METHODS
  The case records of LT recipients, who were nondiabetic, nonhypertensive, and with normal renal parameters prior to LT were retrospectively examined for acute cellular rejection (ACR) episodes and three major adverse effects of tacrolimus, i.e. neurotoxicity, nephrotoxicity, and new onset diabetes mellitus (NODM).
  
  
  RESULTS
  Thirty-two LT recipients fulfilled the criteria for the study. The mean (±SD) tacrolimus level for the 290 troughs (after 10 days) was 8.5 ± 3.8 ng/mL. At 10 days, 1 month, 3 months, and 6 months, the trough values were 7.3 ± 2.9, 9.7 ± 3.4, 7.9 ± 3.3, and 7.6 ± 2.6 ng/mL, respectively. The mean time taken for stabilization of the blood pressure and biochemical parameters was 7 ± 2 days. Overall, a trough window with the least adverse effect was 7 to 7.9 ng/mL. Neurotoxicity was least in the trough range 5 to <8 ng/mL. Symptoms included headache in four, tremors in three, seizure in one, confusion and psychosis in two, and combination in three. Nephrotoxicity was least in trough 8 to <11 ng/mL. One patient progressed to chronic kidney disease at 6 months. NODM was present in 11 % to 18 % across the various trough range, including the extremes (mean trough level, 8.4 ± 4.4 ng/dL). At 6 months, five recipients were on treatment for NODM. Three recipients developed ACR, two within the first month and one at 7 weeks. The trough levels were 8.5, 9, 15.2 ng/mL, respectively. All recovered with three pulse doses of methylprednisolone.
  
  
  CONCLUSIONS
  Tacrolimus concentration of 5 to <8 ng/mL was associated with least overall toxicity, neurotoxicity, and ACR.
authors.affiliation: Department of Hepatology and Liver Transplantation, Global Hospitals and Health City, 439, Cheran Nagar, Perumbakkam, Chennai, 600 100, India, joyvargese@gmail.com.
authors.forename: Joy
authors.initials: J
authors.lastname: Varghese
authors.forename: Mettu Srinivasa
authors.initials: MS
authors.lastname: Reddy
authors.forename: Kota
authors.initials: K
authors.lastname: Venugopal
authors.forename: Rajasekhar
authors.initials: R
authors.lastname: Perumalla
authors.forename: Gomathy
authors.initials: G
authors.lastname: Narasimhan
authors.forename: Olithselvan
authors.initials: O
authors.lastname: Arikichenin
authors.forename: Vivekanandan
authors.initials: V
authors.lastname: Shanmugam
authors.forename: Naresh
authors.initials: N
authors.lastname: Shanmugam
authors.forename: Vijaya
authors.initials: V
authors.lastname: Srinivasan
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Jayanthi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Rela
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003221:Confusion / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006261:Headache / Q000139:chemically induced; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011618:Psychotic Disorders; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced; D012189:Retrospective Studies; D012640:Seizures / Q000139:chemically induced; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*; D014202:Tremor / Q000139:chemically induced; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus
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