title: Pharmacokinetics of tacrolimus co-administered with adefovir dipivoxil to liver transplant recipients.
abstract: BACKGROUND
  Adefovir dipivoxil has activity against wild-type and lamivudine-resistant hepatitis B virus (HBV) and is frequently used to manage HBV infection in transplant recipients. Calcineurin inhibitors are a central component of immunosuppressive therapy.
  
  
  OBJECTIVE
  Study GS-02-531 was an open-label, multicentre drug interaction trial to examine potential drug interactions between adefovir and tacrolimus in stable post-transplant recipients.
  
  
  METHODS
  Sixteen non-HBV-infected post-transplant recipients with median age 45.5 years (69% male, 44% Caucasian, 50% Hispanic and 6% Black) and stable hepatic and renal function on a stable daily dose of tacrolimus (2-10 mg total daily dose) were studied before (tacrolimus alone) and after co-administration of adefovir 10 mg daily for 14 days (Days 1-14). Pharmacokinetic (PK) analyses utilized non-compartmental methods.
  
  
  RESULTS
  The median elimination half-life of tacrolimus was 14.47 and 12.59 h for Day 0 and Day 14 respectively. The geometric mean ratios for tacrolimus on Day 14 vs Day 0 were 105.2% [90% confidence interval (90% CI): 89.8-123%] for C(max) and 106.4% (90% CI: 92.9-122%) for AUC(tau). Both 90% CIs for the ratios were contained within the predefined lack of interaction bounds of 80 and 125% (i.e. within the bounds for the equivalence assessment), indicating that these PK parameters of tacrolimus are not significantly altered by co-administration of adefovir. Similarly, the observed adefovir PK parameters after 14 days of co-administration with tacrolimus were comparable to historical data in non-transplant patients receiving adefovir alone. Serum creatinine values were stable during the study period.
  
  
  CONCLUSIONS
  There is no significant PK interaction between tacrolimus and adefovir co-administered to liver transplant recipients for 14 days.
authors.affiliation: Department of Medicine and Surgery, University of California San Francisco, San Francisco, CA 94143-0538, USA. Norah.Terrault@itsa.ucsf.edu
authors.forename: Norah A
authors.initials: NA
authors.lastname: Terrault
authors.forename: Tram T
authors.initials: TT
authors.lastname: Tran
authors.forename: Eugene
authors.initials: E
authors.lastname: Schiff
authors.forename: Brendan M
authors.initials: BM
authors.lastname: McGuire
authors.forename: Robert S
authors.initials: RS
authors.lastname: Brown
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tupper
authors.forename: Srini
authors.initials: S
authors.lastname: Ramanathan
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Enejosa
authors.forename: Lijie
authors.initials: L
authors.lastname: Zhong
authors.forename: Jian
authors.initials: J
authors.lastname: Zong
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D005260:Female; D006207:Half-Life; D006509:Hepatitis B / Q000517:prevention & control; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D016559:Tacrolimus / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D063065:Organophosphonates; D000225:Adenine; C106812:adefovir dipivoxil; D016559:Tacrolimus