Effect of active infection on cytochrome P450‐mediated metabolism of cyclosporine in renal transplant patients

Hegazy, Sahar K; Adam, Ahmed; Hamdy, Noha Alaa; Khalafallah, Nawal

doi:10.1111/tid.12375

Cited by 5 publications

(7 citation statements)

References 39 publications

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“…The CyA levels after infection resolution were not statistically different from baseline (p = 0.382) in patients [14], and (p = 0.5) in the fungal experiment and (p = 0.482) in the bacterial experiment in rabbits.…”

Section: Comparing Results Of the Clinical And Animal Studiesmentioning

confidence: 73%

“…The infection studies resulted in significant rise in CyA trough level after infection in clinical (p < 0.001, n = 20) [14] and in experimental either fungal (p = 0.018, n = 7) or bacterial (p = 0.005, n = 6) studies respectively, which subsided down to near baseline levels after infection was resolved. The CyA levels after infection resolution were not statistically different from baseline (p = 0.382) in patients [14], and (p = 0.5) in the fungal experiment and (p = 0.482) in the bacterial experiment in rabbits.…”

Section: Comparing Results Of the Clinical And Animal Studiesmentioning

confidence: 97%

“…The present data followed a clinical study in patients, which looked at the effect of active infection on CyA blood level in immunocompromised renal transplant patients [14]. The animal studies were designed to assess the effect of infection on CyA systemic exposure in rabbits.…”

Section: Comparing Results Of the Clinical And Animal Studiesmentioning

confidence: 99%

“…We have recently reported data describing the effect of active infection on CyA blood level in renal transplant patients [14]. To better understand the effect of infection on drug handling in immunosuppressed patients, we have since then evaluated effects of a fungal (Candida) and a bacterial (e-coli) infection on CyA blood level in rabbits.…”

Section: Introductionmentioning

confidence: 99%

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A New Model of Drug-Disease Interaction in Rabbits

Hegazy¹,

Hamdy²,

Adam³

et al. 2017

JPP

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Abstract:Background: Drug-infection interaction should be considered in drug prescribing, particularly if potentiated by co-occuring drug-drug interactions. The effects of Candida and e-coli infections separately, and fluconazole administration were tested on cyclosporine blood level in rabbits. Methods: Three study designs were carried out, crossover single-dose-fluconazole-cyclosporine study testing fluconazole-cyclosporine interaction, multi-dose candida-fluconazole-cyclosporine and multi-dose escherichia coli-cyclosporine study designs involving each rabbit acting as its control; cyclosporine was given daily in both studies. Candida and e-coli infections were inoculated on day 5. In the Multi-Candida-Fluc-CyA, fluconazole-cyclosporine interaction was also considered, and fluconazole was administered daily from day 9-18. In all three studies, Cyclosporine trough levels and serum creatinine were measured by CMIA and enzymatic assay respectively, pre, during, post-infection and after fluconazole administration in the Candida study. Results: Both infections resulted in significant rise in cyclosporine trough level (p = 0.018) and (p = 0.005) in fungal and bacterial studies, respectively. The median rise in CyA level reached 52% (range 9-426%) in the Candida infection and reached 60 ± 47.5% (mean) with the e-coli infection. Fluconazole also increased mean cyclosporine trough levels in the single-dose study by 70.3 ± 45.3 and the concomitant rise in the multi-dose study reached 76% (median, range 22-665%). Conclusions: Cyclosporine trough levels increased during Candida and e-coli infections and also during fluconazole administration in the single and multi-dose studies. Fluconazole exerted an additive effect to the Candida inhibitory effect. Type of infection and inoculum size affected CyA levels differently. Monitoring cyclosporine level during episodes of infection as well as in therapy regimen involving interacting drugs is advisable.

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Section: Comparing Results Of the Clinical And Animal Studiesmentioning

confidence: 73%

Section: Comparing Results Of the Clinical And Animal Studiesmentioning

confidence: 97%

Section: Comparing Results Of the Clinical And Animal Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A New Model of Drug-Disease Interaction in Rabbits

Hegazy¹,

Hamdy²,

Adam³

et al. 2017

JPP

View full text Add to dashboard Cite

show abstract

“…Cuando se administran en forma conjunta ciclosporina y voriconazol, se observa un incremento del área bajo la curva de ciclosporina y una elevación de la concentración sérica de ésta, ocasionada por metabolización oxidativa, que involucra las vías: CYP2C19, CYP2C9 y CYP3A4. Asimismo, voriconazol también actúa como inhibidor de CYP3A4, haciéndolo susceptible a la interacción con ciclosporina, la cual es principalmente metabolizada por la vía del CYP3A4, ocasionando una toxicidad renal, alteraciones electrolíticas y neurotoxicidad, como RAM más agudas [5][6][7][8][9] .…”

Section: Introductionunclassified