A Steady-State Head-to-Head Pharmacokinetic Comparison of All FK-506 (Tacrolimus) Formulations (ASTCOFF): An...

Area of Science:

• Pharmacology
• Nephrology
• Drug Formulation

Background:

• Tacrolimus is a key immunosuppressant in renal transplantation.
• Multiple tacrolimus formulations exist, including immediate-release (IR-Tac), extended-release (ER-Tac), and novel once-daily tablets (LCPT).
• Comparative pharmacokinetic data are essential for guiding formulation switching and dosing.

Purpose of the Study:

• To compare the pharmacokinetics of three innovator tacrolimus formulations in stable renal transplant recipients.
• To establish dose conversion factors between IR-Tac, ER-Tac, and LCPT.

Main Methods:

• A two-sequence, three-period crossover study design was employed.
• Thirty stable renal transplant patients received IR-Tac, ER-Tac, and LCPT for 7 days each.
• Blood samples were collected over 24 hours to determine pharmacokinetic parameters, including Cmax, Tmax, and exposure.

Main Results:

• LCPT demonstrated significantly higher exposure per milligram, lower intraday fluctuation, and a prolonged Tmax compared to both IR-Tac and ER-Tac.
• No significant pharmacokinetic differences were observed between IR-Tac and ER-Tac.
• Recommended daily dose conversion rates were established: IR-Tac:ER-Tac (+8%), IR-Tac:LCPT (-30%), and ER-Tac:LCPT (-36%).

Conclusions:

• LCPT offers a distinct pharmacokinetic profile with improved exposure and reduced fluctuation compared to existing IR-Tac and ER-Tac formulations.
• The established dose conversion factors can aid clinicians in transitioning patients between tacrolimus formulations.
• Further research may explore the clinical implications of these pharmacokinetic differences on long-term outcomes.