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. 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
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Background: The impact of cytochrome P450 3A5 (CYP3A5) genotype of recipients (intestine)as well as donors (graft liver) on the tacrolimus pharmacokinetics and theincidence of infectious complications was assessed in Japanese living-donor livertransplant (LDLT) adult recipients.Material/Methods: Fifty-six patients were divided into 4 groups based on the CYP3A5 genotype (expressionof *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 everymonth until 12 months after LDLT. The incidences of postoperative infectiouscomplication, acute cellular rejection and tacrolimus adverse effect werecompared.Results: The tacrolimus blood concentrations among 4 groups did not significantly differat 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 12months. The C/Ds in EX-R/NEX-D (163.2 at 2 weeks) have been significantlylower 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 inNEX-R/NEX-D (189.3 at 8 months). Additionally, logistic regression analysisshowed that EX-R/EX-D had significantly higher risk for the development of infectiouscomplications than NEX-R/NEX-D (odds ratio 8.67, p=0.03).Conclusions: Preoperative assessment of CYP3A5 genotypes in both recipients and donorswould be useful not only for predicting tacrolimus pharmacokinetics but alsodefining high-risk group of infectious complications after LDLT.
- Annals of transplantation : quarterly of the Polish Transplantation Society
Annals of transplantation : quarterly of the Polish Transplantation Society 16(4), 55-62, 2011-12-30
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