Pharmacokinetics for once-daily versus twice-daily tacrolimus formulations in de novo liver transplantation: A randomized, open-label trial

Lutz Fischer, Pavel Trunečka, Bruno Gridelli, Andre Roy, Alessandro Vitale, Andrés Valdivieso, Evaristo Varo, Daniel Seehofer, Stephen Lynch, Didier Samuel, Bo Goran Ericzon, Karim Boudjema, Carmen Karpf, Nasrullah Undre

Research output: Contribution to journalArticle

Abstract

Tacrolimus, a cornerstone immunosuppressant, is available as a twice-daily formulation (tacrolimus bid). A once-daily prolonged-release formulation (tacrolimus qd) has been developed. This 6-week, randomized, phase 2, multicenter, open-label, prospective trial in primary liver transplant recipients investigated and compared the pharmacokinetics (PK) of tacrolimus for qd and bid formulations. All patients received tacrolimus-based immunosuppression (tacrolimus qd, n = 67; bid, n = 62). PK data were available for 77 patients (tacrolimus qd, n = 45; bid, n = 32). Tacrolimus area under the curve (AUC) from 0 to 24 hours (AUC0-24) at equivalent doses was approximately 50% lower for tacrolimus qd than for bid on day 1 (146 versus 264 ng·h/mL, respectively), but by day 14 was comparable between treatments (324 and 287 ng·h/mL, respectively) with higher tacrolimus qd doses. There was a strong correlation between AUC0-24 and concentration at 24 hours for tacrolimus qd and bid (r = 0.92 and r = 0.76, respectively). Furthermore, the relationship between these 2 parameters (ie, the slope of the line) was also similar for the 2 formulations. Efficacy endpoints were comparable for both formulations at 6 weeks with no marked differences in incidence, nature, or severity of adverse events between treatments (although the study was not powered to draw efficacy conclusions). These results suggest that targeting the same trough levels will achieve similar total AUC over 24 hours for both tacrolimus qd and tacrolimus bid in de novo liver transplant recipients.

Original languageEnglish
Pages (from-to)167-177
Number of pages11
JournalLiver Transplantation
Volume17
Issue number2
DOIs
Publication statusPublished - Feb 2011

ASJC Scopus subject areas

  • Surgery
  • Transplantation
  • Hepatology

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