A single-center, open-label, randomized cross-over study to evaluate the pharmacokinetics and bioavailability of once-daily prolonged-release formulations of tacrolimus in de novo liver transplant recipients
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A single-center, open-label, randomized cross-over study to evaluate the pharmacokinetics and bioavailability of once-daily prolonged-release formulations of tacrolimus in de novo liver transplant recipients. / Herden, Uta; Sterneck, Martina; Buchholz, Bettina M; Achilles, Eike G; Ott, Armin; Fischer, Lutz.
In: IMMUN INFLAMM DIS, Vol. 9, No. 4, 12.2021, p. 1771-1780.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A single-center, open-label, randomized cross-over study to evaluate the pharmacokinetics and bioavailability of once-daily prolonged-release formulations of tacrolimus in de novo liver transplant recipients
AU - Herden, Uta
AU - Sterneck, Martina
AU - Buchholz, Bettina M
AU - Achilles, Eike G
AU - Ott, Armin
AU - Fischer, Lutz
N1 - © 2021 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.
PY - 2021/12
Y1 - 2021/12
N2 - BACKGROUND: The narrow therapeutic window of tacrolimus (Tac) requires intense drug monitoring to achieve adequate efficacy while minimizing dose-related toxicities. Once-daily formulations of Tac (LCP-Tac and PR-Tac) have been recently designed for higher bioavailability and a more consistent exposure over time, as opposed to the twice-daily, administered immediate-release formulation of Tac (IR-Tac).METHODS: This single-center, open-label, randomized cross-over pharmacokinetic (PK) study compares extended-release LCP-Tac with the prolonged-release formulation of tacrolimus (PR-Tac) in adult de novo liver transplant recipients. Eligible patients were screened and randomized 1:1 to the two treatment arms up to 30 days after liver transplantation. Patients were administered either LCP-Tac or PR-Tac for 14 days followed by another 14-day time interval of the other once-daily Tac medication. A 24hr-PK profile was obtained at the end of each time interval.RESULTS: Nine patients (45%) completed the study resulting in a total of 18 Tac PK profiles. Overall, the profile of the mean concentrations indicated a flattened kinetic of LCP-Tac compared to PR-Tac, especially in the first 3 h after drug intake. The average cumulative dose per day to achieve equivalent trough levels was approximately 25% lower for LCP-Tac (8.7 mg) than for PR-Tac (11.7 mg). LCP-Tac resulted in a longer tmax and fewer peak-to-trough fluctuations compared to PR-Tac.CONCLUSION: Despite methodological weaknesses that limit the conclusions, we have found a more consistent drug exposure for LCP-Tac in de novo LT recipients. LCP-Tac demonstrated a greater bioavailability compared to PR-Tac.
AB - BACKGROUND: The narrow therapeutic window of tacrolimus (Tac) requires intense drug monitoring to achieve adequate efficacy while minimizing dose-related toxicities. Once-daily formulations of Tac (LCP-Tac and PR-Tac) have been recently designed for higher bioavailability and a more consistent exposure over time, as opposed to the twice-daily, administered immediate-release formulation of Tac (IR-Tac).METHODS: This single-center, open-label, randomized cross-over pharmacokinetic (PK) study compares extended-release LCP-Tac with the prolonged-release formulation of tacrolimus (PR-Tac) in adult de novo liver transplant recipients. Eligible patients were screened and randomized 1:1 to the two treatment arms up to 30 days after liver transplantation. Patients were administered either LCP-Tac or PR-Tac for 14 days followed by another 14-day time interval of the other once-daily Tac medication. A 24hr-PK profile was obtained at the end of each time interval.RESULTS: Nine patients (45%) completed the study resulting in a total of 18 Tac PK profiles. Overall, the profile of the mean concentrations indicated a flattened kinetic of LCP-Tac compared to PR-Tac, especially in the first 3 h after drug intake. The average cumulative dose per day to achieve equivalent trough levels was approximately 25% lower for LCP-Tac (8.7 mg) than for PR-Tac (11.7 mg). LCP-Tac resulted in a longer tmax and fewer peak-to-trough fluctuations compared to PR-Tac.CONCLUSION: Despite methodological weaknesses that limit the conclusions, we have found a more consistent drug exposure for LCP-Tac in de novo LT recipients. LCP-Tac demonstrated a greater bioavailability compared to PR-Tac.
KW - Adult
KW - Biological Availability
KW - Cross-Over Studies
KW - Drug Administration Schedule
KW - Humans
KW - Immunosuppressive Agents
KW - Liver Transplantation
KW - Tacrolimus
U2 - 10.1002/iid3.537
DO - 10.1002/iid3.537
M3 - SCORING: Journal article
C2 - 34559956
VL - 9
SP - 1771
EP - 1780
JO - IMMUN INFLAMM DIS
JF - IMMUN INFLAMM DIS
SN - 2050-4527
IS - 4
ER -
