Pharmacokinetic Conversion Study of a New Cyclosporine Formulation in Stable Adult Renal Transplant Recipients

Perlı́k, F; Masri, Marwan; Rost, M.; Kamarád, V

doi:10.5507/bp.2005.048

Cited by 11 publications

(13 citation statements)

References 12 publications

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“…Table provides the tabulation of the reported C max and AUC values from the various patient studies and healthy subject clinical pharmacology studies reported in the literature . The prediction of AUC values for cyclosporine was performed using the regression equation:

A U C - italiccyclosporine = italicCmax - italicCyclosporine \times 3.9965 prefix+ 384.5

and the appropriate fold differences were computed (Table ).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic drug monitoring of cyclosporine and area under the curve prediction using a single time point strategy: appraisal using peak concentration data

Srinivas¹

2015

Biopharm & Drug Disp

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There is an ongoing debate on the use of a single concentration time point C2 for therapeutic drug monitoring (TDM) and exposure prediction for cyclosporine. The objective of the present work was to evaluate the relationship between the peak concentration (Cmax ) versus area under the curve (AUC) for cyclosporine. Using published data from renal transplant patients from an 8-12 week study with two formulations, a simple linear regression model represented by AUC - cyclosporine = Cmax - Cyclosporine × 3.9965 + 384.5 (r = 0.9647; p < 0.001) was developed. Using the regression equation, predictions of AUC from the reported Cmax data were performed; the fold difference between observed vs predicted AUC was computed and the root mean square error for the prediction was calculated. While all but one of the predicted AUCs were contained within a 0.5-2-fold difference (99.1%), a greater proportion of the AUC values were predicted within a narrower range of 0.75 to 1.5-fold difference (78.2%), suggesting the utility of Cmax as the right surrogate for predicting the AUC for cyclosporine with a correlation coefficient of 0.8698 (n = 126; p < 0.001) and a RMSE of 26.2%. Since the time to Cmax generally varies from 1 to 2 h, although the results validate the use of C2, there may be an opportunity to explore the suitability of C1 or C1.5 in a prospective study for the purpose of TDM and AUC prediction of cyclosporine.

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A U C - italiccyclosporine = italicCmax - italicCyclosporine \times 3.9965 prefix+ 384.5

and the appropriate fold differences were computed (Table ).…”

Section: Resultsmentioning

confidence: 99%

Therapeutic drug monitoring of cyclosporine and area under the curve prediction using a single time point strategy: appraisal using peak concentration data

Srinivas¹

2015

Biopharm & Drug Disp

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“…5 In that study, the authors reported a higher rejection rate among Equoral users compared with users of the innovator drug. 5 On the basis of published pharmacokinetic data on healthy individuals 6 and on de novo 7 and long-term transplant patients, 8,9 it is hard to corroborate that the high rejection rate in that uncontrolled and flawed trial is related to the generic CsA Equoral. In summary, considering the comparable CsA dose and the comparable CsA trough levels of both cyclosporine formulations in our study, the data presented here support the assumption that both are interchangeable.…”

Section: Discussionmentioning

confidence: 98%

Maintenance immunosuppressive therapy and generic cyclosporine A use in adult renal transplantation: a single center analysis

Diarra

Riegersperger

Säemann

et al. 2010

Kidney International

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At present, solid organ transplantation relies on chronic immunosuppression. Calcineurin inhibitors (CNIs) still remain one of the most important components in current immunosuppressive regimens. However, life-long immunosuppression of transplant recipients is associated with high costs for the individual, health-care systems, and society. Hence, there is an urgent need of generic drugs that have the potential to exert equivalent therapeutic efficacy at a lower cost. Here, we report our findings of the conversion of 59 stable long-term kidney graft recipients from cyclosporine A (CsA) Neoral to CsA Neoimmun/Equoral. All patients displayed a continuous stable graft function after conversion for a follow-up period of 6 months, and no major side effects associated with the use of CsA Neoimmun/Equoral were observed. Also, CsA dose and trough levels did not differ after conversion to CsA Neoimmun/Equoral. These data indicate that conversion of long-term kidney graft recipients from CsA Neoral to CsA Neoimmun/Equoral is safe and effective, making this specific CsA generic a viable option for CNI therapy in stable renal transplant patients.

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“…In patients after renal transplantation, promising study data are available, showing comparable daily cyclosporine doses and levels after the switch to a generic CSA, without significant differences regarding adverse events 7. However, available study data in patients after HTx are extremely limited.…”

Section: Discussionmentioning

confidence: 99%

Conversion to generic cyclosporine A in stable chronic patients after heart transplantation

Kraeuter¹,

Helmschrott²,

Erbel³

et al. 2013

DDDT

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BackgroundCyclosporine A (CSA) is a narrow therapeutic index drug. Available CSA products differ in the constitution of their emulsion. To compare intra-individual differences after a conversion to a generic CSA, a retrospective single-center study was initiated.MethodsTwenty adult stable chronic (>24 months post heart transplant) recipients were included in the present retrospective study. These patients were previously switched from Sandimmune Neoral® to the generic CSA (Equoral®) according to the patients’ preference during the clinical routine. Dose-normalized trough levels (DNL) and trough levels (C0) at 8 months, 4 months, and 2 weeks before the switch were retrospectively compared with the corresponding values at 2 weeks, 4 months, and 8 months after the switch to the generic CSA. Additionally, changes in the routine laboratory parameters, the number of treated rejection episodes, and the adherence to the CSA target levels were compared.ResultsThe mean DNL (adapted to the daily CSA dose in mg) was 0.71±0.26 (ng/mL)/mg on Neoral therapy; on Equoral it was 0.68±0.23 (ng/mL)/mg, (P=0.38). In comparison to the CSA daily dose prior to the conversion, at postconversion, no significant changes of CSA daily dose were observed (Neoral 140.67±39.81 mg versus Equoral 134.58±41.61 mg; P=0.13). No rejection episodes requiring therapy occurred prior to or postconversion (P=0.99). Additionally, no statistically significant changes of routine laboratory parameters regarding the Modification of Diet in Renal Disease or hematological parameters were seen (all P=not significant). No adverse events after the conversion were observed.ConclusionThis study in chronic and stable HTx patients demonstrated no statistically significant differences in the CSA DNL after a conversion to generic CSA (Equoral). The generic CSA was generally well-tolerated. We concluded that a conversion from Neoral to Equoral is safe and clinically feasible in this distinct patient population. However, multiple switches between different generic immunosuppressants must especially be avoided in the interest of patient safety, and close follow-up examinations must be warranted.

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Pharmacokinetic Conversion Study of a New Cyclosporine Formulation in Stable Adult Renal Transplant Recipients

Cited by 11 publications

References 12 publications

Therapeutic drug monitoring of cyclosporine and area under the curve prediction using a single time point strategy: appraisal using peak concentration data

Therapeutic drug monitoring of cyclosporine and area under the curve prediction using a single time point strategy: appraisal using peak concentration data

Maintenance immunosuppressive therapy and generic cyclosporine A use in adult renal transplantation: a single center analysis

Conversion to generic cyclosporine A in stable chronic patients after heart transplantation

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