Reduced Variability of Tacrolimus Trough Level in Once-Daily Tacrolimus-Based Taiwanese Kidney Transplant Recipients With High-Expressive Genotype of Cytochrome P450 3A5

Wu, Ming‐Chi; Chang, Chun-Yuan; Cheng, Chih-Ming; Shu, Kuo‐Hsiung; Chen, C.-H.; Cheng, Chi‐Hung; Yu, T.-M.; Chuang, Ya‐Wen; Huang, Shih Ting; Tsai, Shang‐Feng; Ho, Hao-Chung; Li, J.-R.; Shiu, Yu-Neng; Fu, Yun‐Ching

doi:10.1016/j.transproceed.2013.11.084

Cited by 13 publications

(13 citation statements)

References 10 publications

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“…Others, including Wu et al, did find an influence of genotype, with the most pronounced drop in IPV after switching from IR‐tacrolimus to ER‐tacrolimus in CYP3A5 expressers ( CYP3A5*1/*1 and CYP3A5*1/*3 ). 18 Their study was performed in Taiwan, where almost half of the population is CYP3A5 expresser, whereas in our largely White population this is not more than 15%–20%. 30 Stifft et al also observed a higher reduction in IPV after conversion from IR‐tacrolimus to ER‐tacrolimus in CYP3A5 expressors than in nonexpressors, although the difference was not statistically significant (−5.4% vs. −2.4%, respectively).…”

Section: Discussionmentioning

confidence: 75%

A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients

Bunthof

Al-Hassany

Nakshbandi

et al. 2021

Clinical Translational Sci

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A high intrapatient variability (IPV) in tacrolimus exposure is a risk factor for poor long‐term outcomes after kidney transplantation. The main objective of this trial was to investigate whether tacrolimus IPV decreases after switching patients from immediate‐release (IR)‐tacrolimus to either extended‐release (ER)‐tacrolimus or LifeCyclePharma (LCP)‐tacrolimus. In this randomized, prospective, open‐label, cross‐over trial, adult kidney transplant recipients on a stable immunosuppressive regimen, including IR‐tacrolimus, were randomized for conversion to ER‐tacrolimus or LCP‐tacrolimus, and for the order in which IR‐tacrolimus and the once‐daily formulations were taken. Patients were followed 6 months for each formulation, with monthly tacrolimus predose concentration assessments to calculate the IPV. The IPV was defined as the coefficient of variation (%) of dose corrected predose concentrations. Ninety‐two patients were included for analysis of the primary outcome. No significant differences between the IPV of IR‐tacrolimus (16.6%) and the combined once‐daily formulations (18.3%) were observed (% difference +1.7%, 95% confidence interval [CI] −1.1% to ‒4.5%, p = 0.24). The IPV of LCP‐tacrolimus (20.1%) was not significantly different from the IPV of ER‐tacrolimus (16.5%, % difference +3.6%, 95% CI −0.1% to 7.3%, p = 0.06). In conclusion, the IPV did not decrease after switching from IR‐tacrolimus to either ER‐tacrolimus or LCP‐tacrolimus. These results provide no arguments to switch kidney transplant recipients from twice‐daily (IR) tacrolimus formulations to once‐daily (modified‐release) tacrolimus formulations when the aim is to lower the IPV.

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Section: Discussionmentioning

confidence: 75%

A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients

Bunthof

Al-Hassany

Nakshbandi

et al. 2021

Clinical Translational Sci

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“…23 Similar to other studies, 22,23 this study showed no difference in the occurrence of AEs between the two arms during study follow-up although the definition of hypertension was different from current Hypertension Canada's 2017 guideline. 24 While the trial was not designed to study differences in clinical outcomes, prior studies in adults have reported high (15%-30%) intrapatient variability in tacrolimus trough concentrations 1,25 with individuals with higher variability demonstrating higher risk of rejection and poor graft outcomes. [1][2][3] In another retrospective study, patients with subtherapeutic or supratherapeutic concentrations showed higher incidence of delayed graft function and longer hospital stay compared to those with therapeutic concentrations.…”

Section: Discussionmentioning

confidence: 99%

“…69% participants in the genotype-guided arm achieved stable therapeutic concentrations while only 44% in the standard arm achieved stable therapeutic concentrations within 30 days (P = 0.089). The median time to achieve stable therapeutic concentrations was 18(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) days in those in the genotypeguided arm; however, in the standard dosing arm, median time could not be generated because <50% participants achieved stable therapeutic concentration during study follow-up.…”

mentioning

confidence: 98%

A randomized clinical trial of age and genotype‐guided tacrolimus dosing after pediatric solid organ transplantation

Min

Papaz

Lafrenière-Roula

et al. 2018

Pediatric Transplantation

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“…In a PK study on 97 Japanese kidney transplant recipients, absolute bioavailability was noted to be lower in CYP3A5*1 genotype patients compared to those with the CYP3A5*3/*3 genotype, while relative bioavailability was lower in patients on once-daily tacrolimus compared to those on twice-daily tacrolimus, regardless of CYP3A5 genotype 16. In a similar study among Taiwanese kidney transplant recipients,17 PK assessment was performed in 71 patients with high-expressive genotype (CYP3A5*1/*1 or CYP3A5*1/*3) and 79 patients with low-expressive genotype (CYP3A5*3/*3). Results showed that the tacrolimus trough levels were significantly higher in patients with low-expressive genotype before and after conversion to the once-daily formulation.…”

Section: Once-daily Tacrolimus: Dosing and Pharmacokineticsmentioning

confidence: 93%

Update on the clinical utility of once-daily tacrolimus in the management of transplantation

Salas¹,

Srinivas²

2014

DDDT

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Adherence to immunosuppression and minimizing variability in drug exposure are important considerations in preventing rejection and maximizing overall transplant outcomes. The availability of once-daily tacrolimus may confer potential benefit by simplifying immunosuppressive regimens, thereby improving medication adherence among transplant recipients. Pharmacokinetic studies in healthy normal volunteers and stable transplant recipients suggest that once-daily tacrolimus is bioequivalent to twice-daily tacrolimus. Efficacy studies suggest that once-daily tacrolimus is noninferior to twice-daily tacrolimus with a concentration-dependent rejection risk. The incidence of biopsy-proven acute rejection, graft survival, and patient survival are more or less comparable between the two tacrolimus formulations. Once-daily tacrolimus has also been reported to have favorable effects on blood pressure, lipid profile, and glucose tolerance. Once-daily tacrolimus may be a viable option to consider for de novo immunosuppression or for conversion from conventional tacrolimus.

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Reduced Variability of Tacrolimus Trough Level in Once-Daily Tacrolimus-Based Taiwanese Kidney Transplant Recipients With High-Expressive Genotype of Cytochrome P450 3A5

Cited by 13 publications

References 10 publications

A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients

A randomized crossover study comparing different tacrolimus formulations to reduce intrapatient variability in tacrolimus exposure in kidney transplant recipients

A randomized clinical trial of age and genotype‐guided tacrolimus dosing after pediatric solid organ transplantation

Update on the clinical utility of once-daily tacrolimus in the management of transplantation

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