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

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

Bibliographic Details
Main Author: Hooper, David K.
Language:English
Published: University of Cincinnati / OhioLINK 2010
Subjects:
Surgery
Tacrolimus
Kidney Transplant
Nicardipine
Cytochrome P450
Pharmacogenetics
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-ucin12889826322021-08-03T06:14:20Z The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients Hooper, David K. Surgery Tacrolimus Kidney Transplant Nicardipine Cytochrome P450 Pharmacogenetics 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 bycytochrome 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 12cases 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 caseswho 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 heldper 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. 2010 English text University of Cincinnati / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632 http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632 unrestricted This thesis or dissertation is protected by copyright: some rights reserved. It is licensed for use under a Creative Commons license. Specific terms and permissions are available from this document's record in the OhioLINK ETD Center.
collection NDLTD
language English
sources NDLTD
topic Surgery
Tacrolimus
Kidney Transplant
Nicardipine
Cytochrome P450
Pharmacogenetics
spellingShingle Surgery
Tacrolimus
Kidney Transplant
Nicardipine
Cytochrome P450
Pharmacogenetics
Hooper, David K.
The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients
author Hooper, David K.
author_facet Hooper, David K.
author_sort Hooper, David K.
title The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients
title_short The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients
title_full The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients
title_fullStr The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients
title_full_unstemmed The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients
title_sort impact of cyp3a5 genotype on the interaction between tacrolimus and intravenous nicardipine in kidney transplant recipients
publisher University of Cincinnati / OhioLINK
publishDate 2010
url http://rave.ohiolink.edu/etdc/view?acc_num=ucin1288982632
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