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Effect of coadministered HIV‐protease inhibitors on tacrolimus and sirolimus blood concentrations in a kidney transplant recipients
Author(s) -
Barau Caroline,
Blouin P.,
Creput Caroline,
Taburet A.M.,
Durrbach Antoine,
Furlan Valérie
Publication year - 2009
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/j.1472-8206.2009.00706.x
Subject(s) - tacrolimus , medicine , ritonavir , sirolimus , pharmacology , calcineurin , antibacterial agent , gastroenterology , urology , transplantation , viral load , immunology , chemistry , antibiotics , human immunodeficiency virus (hiv) , biochemistry , antiretroviral therapy
A patient with human immunodeficiency virus infection and end‐stage renal disease received a renal transplant. At the time of surgery, the patient was on quadruple antiretroviral therapy (lamivudine, zidovudine, and amprenavir/ritonavir). Immunosuppression was initiated with basiliximab, corticosteroid, mycophenolate mofetil, and a single 0.5 mg dose of tacrolimus. In the following days, an increase in tacrolimus concentration was observed with a peak of 37 ng/mL. Tacrolimus half‐life was 6.5 days and tacrolimus maintenance dose was 0.5 mg every 4 days. Eleven months later, the patient had developed Kaposi sarcoma. Tacrolimus was replaced by sirolimus (first dose 1 mg), and the patient was stabilized with 1.5 mg of sirolimus once a week. Increased tacrolimus half‐life and increased dose interval of sirolimus and tacrolimus were due to CYP3A4/5 and/or P‐glycoprotein inhibition by protease inhibitors. Close monitoring is required in the management of tacrolimus and sirolimus dosing regimens when combined with ritonavir boosted HIV‐1 protease inhibitors.