PMID- 33751414
OWN - NLM
STAT- MEDLINE
DCOM- 20211028
LR  - 20211028
IS  - 1179-1926 (Electronic)
IS  - 0312-5963 (Linking)
VI  - 60
IP  - 7
DP  - 2021 Jul
TI  - Clinical Impact of the Adaptation of Initial Tacrolimus Dosing to the CYP3A5 
      Genotype After Kidney Transplantation: Systematic Review and Meta-Analysis of 
      Randomized Controlled Trials.
PG  - 877-885
LID - 10.1007/s40262-020-00955-2 [doi]
AB  - OBJECTIVE: The aim of this systematic review and meta-analysis was to compare the 
      clinical outcomes between genotype-guided and conventional tacrolimus doses in 
      kidney transplantation patients. MATERIALS AND METHODS: We performed a 
      comprehensive literature search of the PubMed, EMBASE, and Cochrane databases 
      from the date of inception to 26 February 2020. References of the retrieved 
      articles were also reviewed and any further relevant studies were included. The 
      search terms included 'tacrolimus', 'cytochrome P-450 CYP3A', 'polymorphism, 
      genetic', 'genomics', 'genome', 'genotype', 'genes', 'alleles', and 
      'pharmacogenetics'. RESULTS: Our study showed that the genotype-guided group 
      included an increased proportion of patients with tacrolimus concentrations in 
      the therapeutic range at steady state (risk ratio [RR] 1.40, 95% confidence 
      interval [CI] 1.14-1.72, p = 0.001; high quality), with a trend for achieving 
      therapeutic concentrations earlier compared with those in the conventional group. 
      However, there was no statistical difference in the incidence of delayed graft 
      function (RR 1.98, 95% CI 0.92-1.76, p = 0.12; moderate quality), incidence of 
      acute rejection (RR 1.00, 95% CI 0.64-1.55, p = 1.00; moderate quality), 
      incidence of graft survival censored for death (RR 1.02, 95% CI 0.98-1.06, 
      p = 0.37; moderate quality), and incidence of adverse effects (AEs). CONCLUSIONS: 
      Although the genotype-guided group had a higher proportion of patients within the 
      targeted concentration and less median time to achieve the therapeutic range, the 
      clinical endpoints, including delayed graft function, acute rejection, graft 
      survival censored for death, and AEs were similar in both groups. All in all, 
      evidence suggested there was no utility in pharmacogenetics for tacrolimus based 
      on the cytochrome P450 (CYP) 3A5 genotype. Studies with Chinese and African 
      American populations are needed due to the frequency of genetic polymorphisms of 
      CYP3A5. Furthermore, a dosing algorithm that includes demographic and clinical 
      factors plus multiple genetic variants should be added for consideration, and may 
      optimize early tacrolimus exposure.
FAU - Yang, Hui
AU  - Yang H
AD  - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 
      Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China.
FAU - Sun, Yiqi
AU  - Sun Y
AD  - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 
      Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China.
FAU - Yu, Xiaojia
AU  - Yu X
AD  - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 
      Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China.
FAU - Hu, Xiaopeng
AU  - Hu X
AD  - Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Wang, Wei
AU  - Wang W
AD  - Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Zhang, Xiaodong
AU  - Zhang X
AD  - Department of Urology, Beijing Chao-Yang Hospital, Capital Medical University, 
      Beijing, China.
FAU - Liu, Lihong
AU  - Liu L
AD  - Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 
      Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, China. hongllh@126.com.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20210310
PL  - Switzerland
TA  - Clin Pharmacokinet
JT  - Clinical pharmacokinetics
JID - 7606849
RN  - 0 (Immunosuppressive Agents)
RN  - EC 1.14.14.1 (CYP3A5 protein, human)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP3A)
RN  - WM0HAQ4WNM (Tacrolimus)
SB  - IM
MH  - Cytochrome P-450 CYP3A/genetics
MH  - Dose-Response Relationship, Drug
MH  - Genotype
MH  - Graft Rejection/genetics/prevention & control
MH  - Humans
MH  - Immunosuppressive Agents
MH  - *Kidney Transplantation
MH  - Randomized Controlled Trials as Topic
MH  - *Tacrolimus
EDAT- 2021/03/23 06:00
MHDA- 2021/10/29 06:00
CRDT- 2021/03/22 19:15
PHST- 2020/10/16 00:00 [accepted]
PHST- 2021/03/23 06:00 [pubmed]
PHST- 2021/10/29 06:00 [medline]
PHST- 2021/03/22 19:15 [entrez]
AID - 10.1007/s40262-020-00955-2 [pii]
AID - 10.1007/s40262-020-00955-2 [doi]
PST - ppublish
SO  - Clin Pharmacokinet. 2021 Jul;60(7):877-885. doi: 10.1007/s40262-020-00955-2. Epub 
      2021 Mar 10.