Pharmacokinetics and Pharmacodynamics of Once-Daily Tacrolimus Compared With Twice-Daily Tacrolimus in the Early Stage After Living Donor Liver Transplantation

被引：8

作者：

Iwasaki, Mami ^{[1
,4
]}

Yano, Ikuko ^{[1
,5
]}

Fukatsu, Sachio ^{[1
]}

Hashi, Sachiyo ^{[1
]}

Yamamoto, Yuki ^{[1
]}

Sugimoto, Mitsuhiro ^{[1
]}

Fukudo, Masahide ^{[1
,2
]}

Masuda, Satohiro ^{[1
,3
]}

Nakagawa, Shunsaku ^{[1
]}

Yonezawa, Atsushi ^{[1
]}

Kaido, Toshimi ^{[6
]}

Uemoto, Shinji ^{[6
]}

Matsubara, Kazuo ^{[1
]}

机构：

[1] Kyoto Univ Hosp, Dept Clin Pharmacol & Therapeut, Kyoto, Japan

[2] Asahikawa Med Univ, Dept Pharm & Pharmacol, Asahikawa, Hokkaido, Japan

[3] Kyushu Univ Hosp, Dept Pharm, Fukuoka, Fukuoka, Japan

[4] Kyoto Univ Hosp, Inst Advancement Clin & Translat Sci, Dept Clin Trial Management, Kyoto, Japan

[5] Kobe Univ Hosp, Dept Pharm, Kobe, Hyogo, Japan

[6] Kyoto Univ, Grad Sch Med, Div Hepatobiliary Pancreat Surg & Transplantat, Dept Surg, Kyoto, Japan

来源：

THERAPEUTIC DRUG MONITORING | 2018年 / 40卷 / 06期

关键词：

tacrolimus; LDLT; OD; pharmacokinetics; calcineurin activity; EXTENDED-RELEASE TACROLIMUS; BLOOD-CONCENTRATION; RECIPIENTS; CONVERSION; FORMULATIONS; CYCLOSPORINE; REGIMEN;

D O I：

10.1097/FTD.0000000000000551

中图分类号：

R446 [实验室诊断]; R-33 [实验医学、医学实验];

学科分类号：

1001 ;

摘要：

Background: This study investigates the pharmacokinetics and pharmacodynamics of tacrolimus using the once-daily (OD) formulation in the early stage after living donor liver transplantation (LDLT) in comparison with those using the twice-daily (TD) formulation. Methods: Nine patients undergoing primary LDLT and treated with the OD tacrolimus formulation were included. The trough blood concentration (C-0) of tacrolimus was monitored every day for 3 weeks after LDLT. A time course study of the blood tacrolimus concentrations and calcineurin (CN) phosphatase activity in peripheral blood mononuclear cells was performed 3 weeks after LDLT. Pharmacokinetic and pharmacodynamic parameters were compared with previously reported data using the TD formulation. Results: The interindividual variability in the daily dose of tacrolimus was significantly larger in the OD formulation than in the TD formulation (P < 0.001). In the time course study, the tacrolimus blood concentrations at 4, 8, and 12 hours after administration and the area under the concentration-time curve from 0 to 24 hours (AUC(0-24)) in the OD group were significantly higher than in the TD group, although the C-0 was equivalent. In addition, the C-0 was not significantly correlated with the AUC(0-24) in the OD formulation. The apparent clearance and the pharmacodynamic parameters examined were not significantly different between the OD and TD groups. Conclusions: The C-0 monitoring of the OD formulation may not be optimal in patients at the early stage after LDLT because the C-0 was not correlated with the AUC(0-24). If clinicians target the same C-0 using the OD and TD formulations, the exposure of tacrolimus can be higher in the OD formulation, and excessive immunosuppression should be noted. Particular attention should be paid to the patients in the early stage after LDLT in the use of the OD oral formulation of tacrolimus.

引用

页码：675 / 681

页数：7

共 23 条

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