Tacrolimus pharmacokinetics are influenced by <scp>CYP3A5</scp>, age, and concomitant fluconazole in pediatric kidney transplant patients

Alghamdi, Alaa; Seay, Sallie G.; Hooper, David K.; Varnell, Charles D.; Darland, Leanna K.; Mizuno, Tomoyuki; Lazear, Danielle; Ramsey, Laura B.

doi:10.1111/cts.13571

Cited by 3 publications

(2 citation statements)

References 40 publications

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“…Tacrolimus is an agent with a narrow therapeutic range and is metabolized by CYP3A4/5. Alghamdi et al 6 . analyzed electronic health records to investigate the effect of CYP3A5 metabolism (intermediate and normal metabolizers [M/NM] versus poor metabolizers [PM]) on reaching the Tacrolimus therapeutic range.…”

Section: Drug Development Question Opportunities For Rwe/rwdmentioning

confidence: 99%

“…Alghamdi et al. 6 analyzed electronic health records to investigate the effect of CYP3A5 metabolism (intermediate and normal metabolizers [M/NM] versus poor metabolizers [PM]) on reaching the Tacrolimus therapeutic range. CYP3A5 IM/NM took longer than PM to reach the therapeutic range, had more dose adjustments, and needed >150% of the required daily dose compared with PM.…”

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confidence: 99%

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Translating real‐world evidence/real‐world data

Ravenstijn

2024

Clinical Translational Sci

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Section: Drug Development Question Opportunities For Rwe/rwdmentioning

confidence: 99%

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confidence: 99%

Translating real‐world evidence/real‐world data

Ravenstijn

2024

Clinical Translational Sci

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Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis

Reddy,

Thompson III,

Tuznik

et al. 2024

Medical Mycology

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Coccidioides is an endemic fungus which causes infections ranging from mild respiratory illness to life-threatening disease, and immunocompromised hosts such as solid organ transplant recipients are at higher risk for disseminated infection and mortality. Our center administers fluconazole prophylaxis to kidney transplant recipients residing in geographic areas with higher incidences of coccidioidomycosis. However, because drug-drug interactions occur between triazoles and immunosuppressants used in transplant medicine, we undertook a study to ascertain whether fluconazole prophylaxis was associated with any important safety outcomes in kidney transplant recipients. This retrospective study evaluated patients who had undergone kidney transplantation between 2016-2019. Data on patient demographics, transplant-related clinical information, use of fluconazole prophylaxis (200 mg daily for 6-12 months post-transplant), and patient outcomes were obtained. The primary outcome was mean estimated glomerular filtration rate (eGFR) at 12 months, comparing those who received fluconazole prophylaxis to those who did not. Secondary outcomes included mean eGFR at 3 months, 6 months and 9 months post-transplant, and patient survival, biopsy-proven graft rejection, graft loss, or a new requirement for post-transplant dialysis, all within 12 months post-transplant. The mean eGFR at 12 months was similar between both groups, with 66.4 ml/min/1.73 m² in the fluconazole prophylaxis group vs. 64.3 ml/min/1.73 m² in the non-fluconazole prophylaxis group (p=0.55). Secondary outcomes were similar across both groups. Multivariable linear regression found no significant association between fluconazole use and graft function. Fluconazole prophylaxis for prevention of coccidioidomycosis was not associated with adverse graft outcomes in kidney transplant recipients.

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HDL-C and creatinine levels at 1 month are associated with patient 12-month survival rate after kidney transplantation

Teng,

Hu,

Liu

2023

Pharmacogenetics and Genomics

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Background Many factors affect the survival rate after kidney transplantation, including laboratory tests, medicine therapy and pharmacogenomics. Tacrolimus, mycophenolate mofetil and methylprednisolone were used as an immunosuppressive regimen after kidney transplantation. The primary goal of this study was to investigate the factors affecting the tacrolimus concentrations and mycophenolate mofetil area under the curve of mycophenolic acid AUC-MPA. Secondary goals were to study the association between perioperative period laboratory tests, medicine therapy, CYP3A5 genetic polymorphisms, and survival rate in kidney renal transplant patients. Methods A total of 303 patients aged above 18 years were enrolled in this study. Their clinical characteristics, laboratory tests, and medicine therapy regimens were collected. We followed the patients for survival for 1 year after kidney transplantation. Results Multivariable logistic analyses reveal that age greater than 50 years, and the CY3A5 *3*3 genotype were independently, positively, and significantly related to tacrolimus C/D ratio at 7 days. At 1 month of follow-up, only CYP3A5 *3*3 was associated with tacrolimus C/D ratio. Basiliximab, Imipenem and cilastatin sodium, sex were associated with mycophenolate mofetil AUC-MPA at 7 days. In the COX regression analysis, a high-density lipoprotein cholesterol level≥1 mmol/L was identified as a positive independent risk factors for the survival rate, while a creatinine level ≥200 μmol/L was a negatively independent risk factors for survival rate. Conclusion These results suggest that age, genes, and drug-drug interaction can affect the concentration of tacrolimus.

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Tacrolimus pharmacokinetics are influenced by CYP3A5, age, and concomitant fluconazole in pediatric kidney transplant patients

Cited by 3 publications

References 40 publications

Translating real‐world evidence/real‐world data

Translating real‐world evidence/real‐world data

Safety of fluconazole in kidney transplant recipients for prevention of coccidioidomycosis

HDL-C and creatinine levels at 1 month are associated with patient 12-month survival rate after kidney transplantation

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