CYP3A5*1/*3 genotype influences the blood concentration of tacrolimus in response to metabolic inhibition by ketoconazole

Chandel, Nirupama; Aggarwal, Pardeep K.; Minz, Mukut; Sakhuja, Vinay; Kohli, Krishan K.; Jha, Vivekanand

doi:10.1097/fpc.0b013e32832bd085

Cited by 28 publications

(17 citation statements)

References 26 publications

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“…These include pre-emptive transplantation [27], increased use of peritoneal dialysis as a bridge to transplantation [25], avoidance of use of more expensive immunosuppressive drugs like mycophenolate mofetil in favor of cheaper ones like azathioprine and use of metabolic inhibitors to reduce the dose requirement of calcineurin inhibitors [28]. Insurance should not involve pre-payment by the patient.…”

Section: Discussionmentioning

confidence: 99%

Kidney Transplantation Is Associated with Catastrophic Out of Pocket Expenditure in India

Ramachandran

Jha

2013

PLoS ONE

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Kidney transplantation (KT) is only viable renal replacement option for most patients in India. Most patients do not have health insurance and meet treatment expenditure from their own resources. We prospectively evaluated the expenses associated with KT and its impact on the socioeconomic status of families in a public hospital. All direct and indirect expenses incurred by the patients from the time of diagnosis of chronic kidney disease to KT were recorded. Direct expenses included physician fees, cost of drugs and disposables, dialysis, and expenses on investigations and hospitalization. Indirect expenses included travel, food, stay, and loss of income suffered by the family. Educational dropout and financial loss were also recorded. There were 43 males and 7 females between the ages of 12 and 57 years. Direct expenses ranged from US$ 2,151–23,792 and accounted for two-thirds of the total expenses. Pre-referral hospitalization, dialysis and medication accounted for majority of direct expense. Indirect expenses ranged from US$ 226–15,283. Travel expenses and loss of income accounted for most of indirect expense. About 54%, 8%, and 10% of families suffered from severe, moderate, and some financial crisis respectively. A total of 38 families had job losses, and 1 patient and 12 caregivers dropped out of studies. To conclude, KT is associated with catastrophic out-of-pocket expenditure and pushes a majority of the patients who come for treatment to public hospitals into severe financial crisis. Educational dropout and loss of jobs are other major concerns. Systematic efforts are required to address these issues.

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Section: Discussionmentioning

confidence: 99%

Kidney Transplantation Is Associated with Catastrophic Out of Pocket Expenditure in India

Ramachandran

Jha

2013

PLoS ONE

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“…Several drugs (drug‐drug interactions) are important to consider, especially nondihydropyridine calcium channel blockers and azole antifungals that are commonly coadministered in the transplant population. The drug interaction with the azole antifungals has been reported to be less profound in CYP3A5 expressers . For additional information on tacrolimus drug interactions, see the review by van Gelder .…”

Section: Drug: Tacrolimusmentioning

confidence: 99%

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

Birdwell

Decker

Barbarino

et al. 2015

Clin Pharma and Therapeutics

563

519

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Tacrolimus is the mainstay immunosuppressant drug used after solid organ and hematopoietic stem cell transplantation. Individuals who express CYP3A5 (extensive and intermediate metabolizers) generally have decreased dose-adjusted trough concentrations of tacrolimus as compared to those who are CYP3A5 non-expressers (poor metabolizers), possibly delaying achievement of target blood concentrations. We summarize evidence from the published literature supporting this association and provide dosing recommendations for tacrolimus based on CYP3A5 genotype when known (updates at www.pharmgkb.org).

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“…[6][7][8][9][10][11] For example, CYP2C19 inhibitor fluvoxamine has been shown to increase the areas under the curve (AUCs) of the CYP2C19 substrates omeprazole and lansoprazole in CYP2C19 extensive metabolizers but not in poor metabolizers. 8,[12][13][14] Similarly, CYP2D6 inhibitors paroxetine and quinidine have been shown to significantly increase the AUCs of CYP2D6 substrates flecainide, desipramine and venlafaxine, in CYP2D6 extensive metabolizers but not in poor metabolizers.…”

Section: Introductionmentioning

confidence: 99%

Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: from retrospective to prospective

et al. 2010

Pharmacogenomics J

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The impact of CYP3A5*3, a CYP3A5 nonexpresser genotype, on inhibitory effects of diltiazem on tacrolimus metabolism has not been assessed. In retrospective study, when coadministered with diltiazem, mean increments in dose-adjusted C 0D7 , C max and AUC 0-12 h for tacrolimus were larger in CYP3A5 expressers than in CYP3A5 nonexpressers (48.7 vs 3.7%, 31.7 vs 17.2% and 38.2 vs 18.5%, respectively). Subsequently, a prospective study was carried out, patients were randomized to algorithm-predicted dosing or standard dosing. For CYP3A5 expressers, an algorithm guided by CYP3A5 and diltiazem significantly reduced tacrolimus maintenance dosage (P ¼ 0.009) and improved the accuracy of tacrolimus initial dose, resulting in reduction in out-of-range C 0 after initial dose (P ¼ 0.002) and dose adjustments (P ¼ 0.004). However, for CYP3A5 nonexpressers, primary end points were not achieved, and tacrolimus-sparing effect of diltiazem was not remarkable. Our study results show that CYP3A5 genotype-guided tacrolimus-diltiazem combination is a promising therapy in renal transplant recipients in the early postoperative stage.

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CYP3A51/3 genotype influences the blood concentration of tacrolimus in response to metabolic inhibition by ketoconazole

Cited by 28 publications

References 26 publications

Kidney Transplantation Is Associated with Catastrophic Out of Pocket Expenditure in India

Kidney Transplantation Is Associated with Catastrophic Out of Pocket Expenditure in India

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing

Effects of diltiazem on pharmacokinetics of tacrolimus in relation to CYP3A5 genotype status in renal recipients: from retrospective to prospective

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