Interaction Between Cyclosporine and Fluconazole in Renal Allograft Recipients

Canafax, Daniel M.; Graves, Nina M.; Hilligoss, Donald M.; Carleton, Bruce; Gardner, Mark; Matas, Arthur J.

doi:10.1097/00007890-199105000-00016

Cited by 105 publications

(49 citation statements)

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“…Cyclosporin is extensively metabolized, with the liver being the main site of metabolism. Age and hepatic function can impact on CsA clearance 24 and drugs commonly used in the setting of SCT such as phenytoin, 25 itraconazole, 26 fluconazole 27 and macrolide antibiotics, 28,29 can also influence the metabolism of CsA. For example, phenytoin can reduce CsA concentrations by 50%, 25 via induction of hepatic microsomal enzymes.…”

Section: Pharmacology Of Csamentioning

confidence: 99%

Optimizing the use of cyclosporin in allogeneic stem cell transplantation

Duncan

Craddock

2006

Bone Marrow Transplant

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Section: Pharmacology Of Csamentioning

confidence: 99%

Optimizing the use of cyclosporin in allogeneic stem cell transplantation

Duncan

Craddock

2006

Bone Marrow Transplant

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“…Drugs that have interactions with CsA are generally metabolized by hepatic P-450, and this overlapping metabolic pathway is considered the main mechanism of drug effects on CsA levels. 5,6,38 Physical attributes, such as gender and age, have also been reported related to the serum CsA concentrations. 39,40 As younger people have a more rapid CL and a larger Vss than the elderly, caution with serum CsA doses based on differences in age has been claimed to be required.…”

Section: Discussionmentioning

confidence: 99%

“…1,2 The administration of CsA can be difficult, because it has a narrow therapeutic range and because its serum level can be affected pharmacologically by many substances, such as fluconazole, macrolide antibiotics, and calcium channel blockers. [4][5][6] An increased serum CsA concentration may induce nephrotoxicity and neurotoxicity; decreased concentrations may cause severe acute GVHD. [1][2][3][5][6][7][8] CsA is metabolized primarily by cytochrome P-450 enzymes, which exist in the endoplasmic reticulum, especially high concentrations in hepatocytes and the enterocytes of the intestine.…”

Section: Centration; Conditioning Regimen; Drug Interactionmentioning

confidence: 99%

“…[4][5][6] An increased serum CsA concentration may induce nephrotoxicity and neurotoxicity; decreased concentrations may cause severe acute GVHD. [1][2][3][5][6][7][8] CsA is metabolized primarily by cytochrome P-450 enzymes, which exist in the endoplasmic reticulum, especially high concentrations in hepatocytes and the enterocytes of the intestine. 4 In P-450 enzymes, P-450 3A4 predominantly metabolizes CsA, and this enzyme family is subjected to both induction and inhibition by several agents.…”

Section: Centration; Conditioning Regimen; Drug Interactionmentioning

confidence: 99%

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Effect of cyclophosphamide on serum cyclosporine levels at the conditioning of hematopoietic stem cell transplantation

Nagamura

Takahashi

Takeuchi

et al. 2003

Bone Marrow Transplant

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Summary:We retrospectively analyzed the factors that affect serum cyclosporine (CsA) concentrations up to day 14 after allogeneic hematopoietic stem cell transplantation (HSCT). In all, 103 transplant recipients who received MTX and CsA for acute GVHD prophylaxis were analyzed. No significant relationships between serum CsA concentrations and gender, age, serum creatinine levels, AST/ALT levels, or antibiotic/fluconazole administration were found by comparing median CsA concentrations or by using longitudinal or regression multivariate analyses. However, the mean of the median serum CsA concentration in patients (n ¼ 54) receiving the regimen containing cyclophosphamide (CY) (149.7 ng/ml; 95% confidence interval (CI): 132.1-167.4) was significantly (Po0.0001) lower than that in patients (n ¼ 49) receiving the non-CY regimen (217.3 ng/ml; 95% CI: 198.9-235.6). Longitudinal analysis and regression multivariate analysis showed that only administration of CY had a significant effect on the serum CsA concentration. Our results suggest that administration of CY during conditioning can reduce the effects on serum CsA concentrations during the 2 weeks following HSCT. The mechanism of this effect is not clear, but it may be due to the autoinduction of CY.

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“…CsA is widely known as a substrate of CYP3A and P-glycoprotein. It has also been reported that Fcz significantly increases CsA bioavailability and may make it difficult to control CsA blood concentrations in human renal transplant patients treated with CsA-based immunosuppression [5,30]. In humans, CsA nephrotoxicity is well known as a side effect, and this makes the therapeutic range of CsA quite narrow.…”

mentioning

confidence: 99%

Effect of Multiple Oral Dosing of Fluconazole on the Pharmacokinetics of Cyclosporine in Healthy Beagles

Katayama

Igarashi

Tani

et al. 2008

The Journal of Veterinary Medical Science

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ABSTRACT. Fluconazole (Fcz) is successfully used in human organ transplant patients as an antifungal therapy. However, Fcz can increase the cyclosporine (CsA) trough level and lead to CsA nephrotoxicity. In canine renal transplantation, CsA has been used as a major immunosuppressant, and it is important to control its trough level. However, the interaction of Fcz with CsA has not yet been reported in dogs. In this study, the effect of Fcz treatment on the pharmacokinetics of CsA in four healthy beagles was investigated using a fourperiod crossover design. The treatments included CsA alone (A), CsA + multiple-dose Fcz 50 mg (B), CsA + multiple-dose Fcz 25 mg (C) and CsA + single-dose Fcz 50 mg (D). Blood CsA concentrations were measured at 0.5, 1, 2, 4, 6, 8, 10, 12 and 24 hr after CsA administration. The AUC 0-12 and C max values for treatment B were significantly higher than those for the other treatments. In particular, the AUC 0-12 of treatment B was about two times higher than that of treatment A. Fcz administration did not significantly prolong the half-life or mean residence time of CsA. The results of our study show that administration of multiple therapeutic doses of Fcz can significantly increase the CsA blood concentration, which might partially depend upon the Fcz blood concentration. When Fcz is used in CsA-based canine renal transplantation, it may be necessary to adjust the CsA trough level by decreasing the dose.

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Interaction Between Cyclosporine and Fluconazole in Renal Allograft Recipients

Cited by 105 publications

References 0 publications

Optimizing the use of cyclosporin in allogeneic stem cell transplantation

Optimizing the use of cyclosporin in allogeneic stem cell transplantation

Effect of cyclophosphamide on serum cyclosporine levels at the conditioning of hematopoietic stem cell transplantation

Effect of Multiple Oral Dosing of Fluconazole on the Pharmacokinetics of Cyclosporine in Healthy Beagles

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