ImmunosuppressionsEffects of rifampin on cyclosporine disposition in kidney recipients with tuberculosis
Section snippets
Patients and methods
This study included four patients (three men and one woman; weight range 49 to 81 kg; age range 35 to 51 years; 12 to 72 months after kidney transplantation). All patients were treated with a triple immunosuppressive regimen consisting of CyA, azathioprine, and prednisone. Two patients had pulmonary Tbc, one patient had biopsy-proven Tbc pleurisy, and one patient had renal Tbc. They were administered isoniazid, RFP, ethambutol, and pyrazinamide. A dosage of 600 mg of RFP was given daily to all
Results
The blood pharmacokinetic parameter estimates of individual subjects with and without RFP are shown in Table 1. Statistically significant decreases were seen in blood CyA pharmacokinetic parameters, including the following: AUC (ng/mL per hour) (4582.95 ± 239.71 vs 2790.48 ± 251.34), t1/2(h) (3.35 ± 0.12 vs 2.80 ± 0.28) before and after RFP therapy, respectively. The CyA blood clearance increased significantly (0.37 ± 0.03 vs 1.24 ± 0.14) after RFP administration. No significant changes were
Discussion
Cyclosporine is a widely used immunosuppresant to prevent organ rejection. The susceptibility to infections such as Mycobacterium tuberculosis is one of the complications of long-term immunosuppression. Conventional treatment for Tbc usually uses a combination chemotherapy, including RFP. It is well established that RFP is a complex macrocyclic zwitterion that has properties of hepatic enzyme induction. Drug interaction studies have shown that RFP and other agents affected the hepatic
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Cited by (21)
The role of drug-drug interactions in prostate cancer treatment: Focus on abiraterone acetate/prednisone and enzalutamide
2017, Cancer Treatment ReviewsCitation Excerpt :A safe approach could be the substitution with alternative drugs (i.e., warfarin with dabigatran); alternatively, a TDM should be performed (e.g., intensive INR monitoring in patients co-treated with enzalutamide and warfarin). Concerning immunosuppressive drugs, although direct demonstration of PK DDI with enzalutamide is not available, the well-described rifampin-cyclosporine DDI [102] suggests that close monitoring of immunosuppressant drug levels and dose adjustments is a rational approach whenever enzalutamide is administered to a patient taking cyclosporine for the prophylaxis of graft rejection. Likewise, a significant decrease in tacrolimus plasma levels are observed after rifampin administration [103].
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2001, Transplantation ProceedingsMycobacterial infections in patients with chronic renal disease
2001, Infectious Disease Clinics of North AmericaCitation Excerpt :Rifampin, therefore, is given in usual doses in renal failure. Rifampin induces the cytochrome oxidase P-450 system which increases the clearance of corticosteroids two-fold,15 cyclosporine two- to five-fold,3,17,59 and tacrolimus ten-fold,21 requiring higher doses of these immunosuppressive agents. For this reason, some authors replace rifampin with rifabutin, PZA25 or EMB in patients receiving kidney transplants to save on the substantial expense of cyclosporine.
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