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The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients

Hooper, David K.
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632

Abstract Details

2010, MS, University of Cincinnati, Medicine: Clinical and Translational Research.
Tacrolimus (TAC) is prescribed for immunosuppression in the majority of solid organ transplant recipients, yet overexposure can cause acute and chronic kidney injury. Continuous intravenous nicardipine (CIVN) for the treatment of post-transplant hypertension inhibits TAC metabolism by cytochrome P450 (CYP) 3A4. We hypothesized that CIVN in TAC-treated patients would lead to TAC overexposure in patients who genetically lack the alternative pathway for TAC metabolism, CYP3A5. We compared maximum 12-hour TAC trough (MaxC0) and dose-adjusted MaxC0 in 12 cases treated with CIVN immediately following kidney transplantation with 26 controls who were not treated with CIVN. CYP3A5 genotype was determined for all cases. The eight cases who do not express CYP3A5 (CYP3A5*3/*3) had higher median MaxC0 (24.3 ng/ml) than the four cases who do express CYP3A5 (CYP3A5*1/*1) (13.9 ng/ml, p=0.28) and the 26 controls (14.6 ng/ml, p=0.003). Time to MaxC0 was half as long in CYP3A5*3/*3 cases than in the other two groups combined (36 vs. 72 hours, p=0.002) and significantly more scheduled TAC doses were held per patient (1.75 vs. 0.4, p=0.007). Dose-adjusted MaxC0 was likewise higher for CYP3A5*3/*3 cases than the two other groups combined (p=0.02). Six of eight (75%) CYP3A5*3/*3 cases had potentially toxic MaxC0 (> 20 ng/ml) compared to none of four CYP3A5*1/*1 cases and three of 26 (11.5%) controls (p<0.001, CYP3A5*3/*3 cases vs. all others). Thus CYP3A5 nonexpressors who are treated with CIVN are at increased risk for TAC levels in the toxic range. Well designed clinical studies should be carried out to further characterize the clinical implications of this interaction.
Paul Succop, PhD (Committee Chair)
Jens Goebel, MD (Committee Member)
Mark Mitsnetes, MD (Committee Member)
Erin Nicole Haynes, PhD (Committee Member)
30 p.
Surgery
Tacrolimus; Kidney Transplant; Nicardipine; Cytochrome P450; Pharmacogenetics

Recommended Citations

Citations

  • Hooper, D. K. (2010). The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632

    APA Style (7th edition)

  • Hooper, David. The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients. 2010. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632.

    MLA Style (8th edition)

  • Hooper, David. "The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients." Master's thesis, University of Cincinnati, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632

    Chicago Manual of Style (17th edition)

ucin1288982632
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© 2010, some rights reserved.Creative Commons License The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients by David K. Hooper is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by University of Cincinnati and OhioLINK.