Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients

Li, D.; Lu, Wei; Zhu, Jinmin; Gao, Jie; Lou, Ya-Qing; Zhang, G.‐L.

doi:10.1111/j.1365-2710.2007.00850.x

Cited by 67 publications

(69 citation statements)

References 21 publications

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Section: Treated With Steroidssupporting

confidence: 77%

“…Subjects homozygous for the variant * 3, likely owing to the lower metabolic drug clearance, require a lower tacrolimus dose to reach the desired therapeutic levels compared to the subjects with at least one * 1 copy who are considered to express the functional enzyme (21,40,41). Similar results have been previously reported for liver (8,(41)(42)(43), kidney (12,(44)(45)(46)(47), heart (48), and lung recipients (49). In particular, as regards to liver transplantation, our data support the primary importance of the donor with respect to the CYP3A5 genotype (8,43,(50)(51)(52)(53); however, they suggest a possible influence of the recipient genotype also (52), which might be corroborated by the known metabolic role of CYP3A5 in extra-hepatic tissues such as the intestine (51,53).…”

Section: Treated With Steroidsmentioning

confidence: 99%

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Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

et al. 2011

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Abstract. Tacrolimus is a substrate of cytochrome P4503A (CYP3A) enzymes as well as of the drug transporter ABCB1. We have investigated the possible influence of CYP3A5 and ABCB1 single nucleotide polymorphisms (SNPs) and other factors (e.g. albumin, hematocrit and steroids) on tacrolimus blood levels achieved in a population of Caucasian liver (n=51) and kidney (n=50) transplant recipients. At 1, 3 and 6 months after transplantation, tacrolimus doses (mg/kg/day) and trough blood levels (C 0 ) were recorded and the weight-adjusted tacrolimus dosage (mg/kg/day) was calculated. Polymerase chain reaction followed by restriction fragment length polymorphism analysis was used for genotyping CYP3A5 For the G2677T/A and C3435T polymorphisms the total frequencies of the allelic variants T/A and T were 44.7 and 46.7%, respectively. At 1, 3 and 6 months after transplantation the dose-adjusted C 0 levels were significantly lower in patients with one copy of the * 1 allele compared to those homozygous for the * 3 allele. In the case of liver transplant patients the tacrolimus dose requirements were dominantly influenced by the polymorphisms of the CYP3A5 gene in the donors. With regard to the ABCB1 SNPs, in general they did not show any appreciable influence on tacrolimus dosing requirements; however, kidney transplant recipients carrying the 2677T/A allele required significantly higher daily tacrolimus doses than subjects homozygous for the wild-type allele. Identification of CYP3A5 single nucleotide polymorphisms prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus in the patients.

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Section: Treated With Steroidssupporting

confidence: 77%

Section: Treated With Steroidsmentioning

confidence: 99%

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

et al. 2011

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“…In this study, the estimated CL/F of 19.5 L/h was found ( Figure 1 and Figure 2) to be in good correspondence with the previous reported value of 22.9 L/h although the V/F of 380 L was lower than the previously reported one [24,[26][27][28][29][30][31][32]. This is explained by that a lot of previous studies were done in liver transplantation patients possibly with impaired hepatic function.…”

Section: Discussionsupporting

confidence: 68%

Population Pharmacokinetic Analysis of Oral Tacrolimus in Patients with Glomerulonephritis

Shim¹,

Kim²,

Choi³

et al. 2016

Int J Clin Pharmacol Pharmacother

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Objective: Tacrolimus as an immunosuppressant is used to treat for several types of glomerulonephritis. Narrow therapeutic window and huge interindividual variability of tacrolimus make it impossible to predict its serum level. Hence, the purpose of this study was to derive population pharmacokinetic model for tacrolimus in glomerulonephritis patients. Materials and methods: Adult patients diagnosed with glomerulonephritis and treated with oral tacrolimus were included. Electronic medical records were reviewed retrospectively to access clinical findings and demographic data. Population pharmacokinetics of tacrolimus was evaluated using nonlinear mixed effect model by first-order conditional estimation with interaction algorithm. Results: One hundred and forty-five patients were included in this study and one thousand and nine hundreds thirty-eight blood samples were analyzed. The estimated apparent clearance (CL/F) was 19.5 L/h, and apparent volume of distribution (V/F) was 380 L. The final model suggested that serum creatinine levels were negatively correlated with both CL/F and V/F whereas serum albumin levels were positively associated with V/F. Conclusion: Various factors affecting tacrolimus pharmacokinetics were explored. The findings of this study pointed out that tacrolimus pharmacokinetics were related to patients' kidney function and serum albumin level in glomerulonephritis patients. Developed model may guide individualized tacrolimus therapy in glomerulonephritis patients and improve therapeutic outcomes in glomerulonephritis patients.

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“…The majority of studies did not find an association between the ABCB1 3435C>T SNP and tacrolimus pharmacokinetics. [28][29][30][31][32] In this study, we failed to demonstrate that interindividual variation in tacrolimus daily dosage requirements with ABCB1 and CYP3A5 gene polymorphisms in Iranian liver transplant recipients. However, it should be mentioned that liver donor genotype influences tacrolimus pharmacokinetics far more than do the genotypes of the recipient with regard to expression of CYP3A5.…”

Section: Discussionmentioning

confidence: 66%

Association Between Tacrolimus Concentration and Genetic Polymorphisms of CYP3A5 and ABCB1 During the Early Stage After Liver Transplant in an Iranian Population

Rahsaz

Azarpira²,

Nikeghbalian³

et al. 2012

Exp Clin Transplant

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Objectives: Tacrolimus is widely used as an immunosuppressive drug in liver transplant recipients with a narrow therapeutic range and variable individualized pharmacokinetics. Tacrolimus is a substrate of cytochrome P-450 3A enzyme and the drug transporter, P-glycoprotein. Materials and Methods: We determined the genotypic frequencies of cytochrome P-4503A5 (rs776746), and ABCB1 (rs1045642), single nucleotide polymorphisms in a population of 100 Iranian liver transplant patients, and investigated the influence of the above-mentioned single nucleotide polymorphisms on tacrolimus concentrations. At 7 and 30 days after transplant, tacrolimus dosages (mg/kg/d), trough blood levels (T0), and dose-adjusted concentrations (concentration/dosage ratio) were determined. Polymerase chain reaction, followed by restriction fragment length polymorphism analysis, was used for genotyping cytochrome P-4503A5*3 [6986A>G] as well as ABCB1 [3435C>T]. Results: Ninety-five percent of the population showed a cytochrome P-4503A5*3/*3 genotype. ABCB13435TT genotype was observed in 33 cases (33%); whereas 51 cases (51%) carried 3435CT, and 16 cases (16%) carried 3435CC. With regard to the ABCB1 and cytochrome P-4503A5, they showed no influence on tacrolimus dosing requirements at 1 week or 1 month after transplant. No association of any genetic variant with the acute rejection rate was found. Conclusions: Finally, as the liver donor genotype influences tacrolimus pharmacokinetics with regard to expression of cytochrome P-4503A5, far more than the genotype of the recipient; therefore, it should be considered before recommending any personal immunosuppressive treatment based on pharmacogenetics.

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Population pharmacokinetics of tacrolimus and CYP3A5, MDR1 and IL-10 polymorphisms in adult liver transplant patients

Abstract: The TBIL in patients and CYP3A5*3 genetic polymorphism in both donors and recipients contribute to the inter-individual variability of oral tacrolimus apparent clearance in Chinese adult liver transplant patients.

Cited by 67 publications

References 21 publications

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients

Population Pharmacokinetic Analysis of Oral Tacrolimus in Patients with Glomerulonephritis

Association Between Tacrolimus Concentration and Genetic Polymorphisms of CYP3A5 and ABCB1 During the Early Stage After Liver Transplant in an Iranian Population

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