title: Pharmacokinetics for once- versus twice-daily tacrolimus formulations in de novo kidney transplantation: a randomized, open-label trial.
abstract: Tacrolimus, a cornerstone immunosuppressant, is widely available as a twice-daily formulation (Tacrolimus BID). A once-daily prolonged-release formulation (Tacrolimus QD) has been developed that may improve adherence and impart long-lasting graft protection. This study compared the pharmacokinetics (PK) of tacrolimus in de novo kidney transplant patients treated with Tacrolimus QD or Tacrolimus BID. A 6-week, open-label, randomized comparative study was conducted in centers in Europe and Australia. Eligible patients received Tacrolimus QD or Tacrolimus BID. PK profiles were obtained following the first tacrolimus dose (day 1), and twice under steady-state conditions. As secondary objectives, efficacy and safety parameters were also evaluated. Sixty-six patients completed all PK profiles (34 Tacrolimus QD, 32 Tacrolimus BID). Mean AUC(0-24) of tacrolimus on day 1 was approximately 30% lower for Tacrolimus QD than Tacrolimus BID (232 and 361 ng.h/mL, respectively), but was comparable by day 4. There was a good correlation and a similar relationship between AUC(0-24) and C(min) for both formulations. Efficacy and safety data were also comparable over the 6-week period. Tacrolimus QD can be administered once daily in the morning on the basis of the same systemic exposure and therapeutic drug monitoring concept as Tacrolimus BID.
authors.affiliation: Szpital Uniwersytecki, Bydgoszcz, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Wlodarczyk
authors.forename: J-P
authors.initials: JP
authors.lastname: Squifflet
authors.forename: M
authors.initials: M
authors.lastname: Ostrowski
authors.forename: P
authors.initials: P
authors.lastname: Rigotti
authors.forename: S
authors.initials: S
authors.lastname: Stefoni
authors.forename: F
authors.initials: F
authors.lastname: Citterio
authors.forename: Y
authors.initials: Y
authors.lastname: Vanrenterghem
authors.forename: B K
authors.initials: BK
authors.lastname: Krämer
authors.forename: D
authors.initials: D
authors.lastname: Abramowicz
authors.forename: F
authors.initials: F
authors.lastname: Oppenheimer
authors.forename: F
authors.initials: F
authors.lastname: Pietruck
authors.forename: G
authors.initials: G
authors.lastname: Russ
authors.forename: C
authors.initials: C
authors.lastname: Karpf
authors.forename: N
authors.initials: N
authors.lastname: Undre
mesh_terms: D000328:Adult; D000368:Aged; D003692:Delayed-Action Preparations; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000188:drug therapy*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D003692:Delayed-Action Preparations; D007166:Immunosuppressive Agents; D016559:Tacrolimus