Comparing the pharmacokinetics of extended-release tacrolimus (LCP-TAC) to immediate-release formulations in kidney transplant patients

ABSTRACT

Introduction

One of the most commonly used immunosuppressants in organ transplant, tacrolimus exhibits wide interpatient and intrapatient variability and narrow therapeutic index that necessitates routine concentration monitoring and dosage adjustments. Availability of modified -release tacrolimus products offer once-daily dosing options. The objective of this review is to highlight and compare available pharmacokinetic (PK) data of extended-release tacrolimus tablets (LCP-TAC) to immediate-release tacrolimus (IR-TAC) in kidney transplant recipients.

Areas covered

A review of the literature was performed using PubMed and Embase search to identify relevant articles evaluating PK data for LCP-TAC compared to IR-TAC in kidney transplant patients including special populations.

Expert Opinion

LCP-TAC’s unique PK profile may be more favorable than IR-TAC. While the clinical impact of these PK differences have not been established, several outcomes are being evaluated in ongoing studies. Results of these studies will add information incrementally to care for kidney transplant patients. Larger prospective studies evaluating kidney and patient survival differences are needed but it is unlikely that they will be conducted. Given that the patent exclusivity of LCP-TAC for the next several years and imminent loss of exclusivity of PR-TAC, our opinion is the use of LCP-TAC will be increasing, especially in Europe.

KEYWORDS:

• Extended-release
• immunosuppressive drugs
• kidney
• LCP
• pharmacokinetic
• tacrolimus
• transplantation

Article highlights

• LCP-TAC demonstrates unique PK characteristics compared to IR-TAC.

• Key PK differences include lower peak or maximum concentration (Cmax), longer time to maximum concentration (Tmax), less fluctuation between peaks and troughs, and similar overall drug exposure at a reduced dose compared to IR-TAC.

• Due to differences in absorption, LCP-TAC, PR-TAC and IR-TAC are not bioequivalent.

• Further research regarding clinical implications of the pharmacokinetic differences of IR-TAC and LCP-TAC are ongoing.

This box summarizes key points contained in the article.

Declaration of interest

S Bunnapradist has received grant/ research support from: the FDA, NIDDK, NIAID, NIH, Astellas, Mallinckrodt, Bristol-Myers Squibb, CareDx, Natera, Merck, Sanofi, Veloxis, Vitaeris and OneLegacy Foundation, Novartis, Genentech, and TGI Eurofin: and is on the advisory board for Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosure

A reviewer has disclosed that they have previously received research funding from Astellas and Chiesi for work on Tacrolimus. No other peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Author contributions

TT conducted literature review. TT and SB contributed to the outline, drafting, and edits for the manuscript and supporting tables.

Additional information

Funding

This paper was not funded.