Impact of CYP3A5 genotype of recipients as well as donors on the tacrolimus pharmacokinetics and infectious complications after living-donor liver transplantation for Japanese adult recipients.
BACKGROUND
The impact of cytochrome P450 3A5 (CYP3A5) genotype of recipients (intestine) as well as donors (graft liver) on the tacrolimus pharmacokinetics and the incidence of infectious complications was assessed in Japanese living-donor liver transplant (LDLT) adult recipients.


METHODS
Fifty-six patients were divided into 4 groups based on the CYP3A5 genotype (expression of *1 allele: expressor (EX) and non-expressor (NEX)) in each recipients (R) and donors (D), EX-R/EX-D (n=9), EX-R/NEX-D (n=7), NEX-R/EX-D (n=12) and NEX-R/NEX-D (n=28). Tacrolimus blood concentration and concentration/dosage ratio (C/D) were evaluated every week until 4 weeks and every month until 12 months after LDLT. The incidences of postoperative infectious complication, acute cellular rejection and tacrolimus adverse effect were compared.


RESULTS
The tacrolimus blood concentrations among 4 groups did not significantly differ at each follow-up time period. The C/Ds were significantly lower in EX-R/EX-D (median: 122.3 at 2 weeks) than in NEX-R/NEX-D (389.6 at 2 weeks) until 12 months. The C/Ds in EX-R/NEX-D (163.2 at 2 weeks) have been significantly lower than those in NEX-R/NEX-D until 6 months. Over 6 months, however, those in NEX-R/EX-D showed lower levels (84.1 at 8 months) than those in NEX-R/NEX-D (189.3 at 8 months). Additionally, logistic regression analysis showed that EX-R/EX-D had significantly higher risk for the development of infectious complications than NEX-R/NEX-D (odds ratio 8.67, p=0.03).


CONCLUSIONS
Preoperative assessment of CYP3A5 genotypes in both recipients and donors would be useful not only for predicting tacrolimus pharmacokinetics but also defining high-risk group of infectious complications after LDLT.
Department of Pharmacy, Mie University Hospital, 2-174 Edobachi, Tsu, Mie, Japan.
Yuichi
Y
Muraki
Masanobu
M
Usui
Shuji
S
Isaji
Shugo
S
Mizuno
Kaname
K
Nakatani
Tomomi
T
Yamada
Takuya
T
Iwamoto
Shinji
S
Uemoto
Tsutomu
T
Nobori
Masahiro
M
Okuda
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics*; D007239:Infections / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D007564:Japan; D016031:Liver Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D012307:Risk Factors; D016559:Tacrolimus / Q000493:pharmacokinetics*; D055815:Young Adult
D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus