title: Betel Nut Chewing Is Associated With Reduced Tacrolimus Concentration in Taiwanese Liver Transplant Recipients.
abstract: OBJECTIVE
  Studies have shown that arecoline, the major alkaloid component of betel nuts, alters the activity of enzymes in the cytochrome P450 (CYP-450) family. Tacrolimus, an immunosuppressant that protects against organ rejection in transplant recipients, not only is mainly metabolized by CYP3A enzymes but also has a narrow therapeutic range. We aimed to investigate whether dose-adjusted blood trough levels of tacrolimus differed over time between betel nut-chewing and non-betel nut-chewing liver transplant recipients.
  
  
  METHODS
  In this retrospective case-control study, 14 active betel nut-using liver recipients were matched at a 1:2 ratio to 28 non-betel nut-using liver recipients by sex, age, graft source, duration of follow-up after liver transplantation, and estimated glomerular filtration rate. Differences in liver function index, renal function index, and dose-adjusted blood trough levels of tacrolimus over an 18-month period were compared between the 2 groups by using the Generalized Estimating Equation approach.
  
  
  RESULTS
  Dose-adjusted blood trough levels of tacrolimus tended to be significantly (P = .04) lower in betel nut chewers (mean = 0.81, medium = 0.7, 95% confidence interval [CI] = 0.73 to 0.90) than in nonchewers (mean = 1.12, medium = 0.88, 95% CI = 1.03 to 1.22) during the 18-month study period. However, there was no significant difference in renal and liver function index between the 2 groups.
  
  
  CONCLUSIONS
  Liver transplant recipients receiving tacrolimus tend to have lower blood trough levels of the drug over time if they chew betel nuts.
authors.affiliation: Department of Pharmacy, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: W-Y
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: C-Y
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: P-Y
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: C-E
authors.initials: CE
authors.lastname: Hsieh
authors.affiliation: Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: C-J
authors.initials: CJ
authors.lastname: Ko
authors.affiliation: Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: K-H
authors.initials: KH
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: C-C
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Transplantation Center, Third Xiangya Hospital of Central South University, Changsha, China.
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Ming
authors.affiliation: Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan; Transplant Medicine & Surgery Research Centre, Changhua Christian Hospital, Changhua, Taiwan; Transplantation Center, Third Xiangya Hospital of Central South University, Changsha, China; School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. Electronic address: 31560@cch.org.tw.
authors.forename: Y-L
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000328:Adult; D001114:Areca / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D041743:Herb-Drug Interactions; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D008409:Mastication; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000493:pharmacokinetics*; D013624:Taiwan; D066027:Transplant Recipients; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus