Equoral, new cyclosporine drug delivery system, versus neoral: a bioequivalence study in healthy volunteers

Andrýsek, Tomáš; Masri, Marwan; Jegorov, A.; Veselsky, Z; Matha, V.

doi:10.1016/s0041-1345(02)03924-6

Cited by 15 publications

(11 citation statements)

References 3 publications

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“…Our study supports the role of Equoral as an effective and safe calcineurin inhibitor. These findings are in agreement with those of several other studies that identified good results with Equoral treatment in the prevention of acute rejection and patient and graft survival after renal transplantation 6, 7, 13…”

Section: Discussionsupporting

confidence: 93%

“…Several bioequivalence studies with a total of 278 healthy volunteers and a pharmacokinetic conversion study with 70 stable adult renal transplant recipients compared the brand leader Neoral with Equoral. The results of these studies corresponded to bioequivalence criteria and demonstrated that both drugs, Equoral and Neoral, are bioequivalent and interchangeable in stable renal transplant recipients 6–8…”

mentioning

confidence: 73%

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Efficacy of Equoral in Prophylactic Immunosuppression after De Novo Kidney Transplantation

Zadrazil¹,

Jabry²,

Horák³

et al. 2007

Dialysis & Transplantation

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BACKGROUND Cyclosporin A is a well‐known calcineurin inhibitor that has been used for prophylactic immunosuppression after organ transplantation. The aim of this study was to evaluate the efficacy and safety of a new generic cyclosporin formulation, Equoral (Teva Pharmaceuticals), in the treatment of de novo renal transplant recipients. METHODS Twenty cadaveric‐donor renal transplant recipients between 23 and 71 years of age at the time of transplantation (mean age 52 ± 12.5 years) were followed for 12 months to determine if the grafts functioned and if there were rejection attacks and side effects. In addition to cyclosporin, all patients received mycophenolate mofetil (CellCept) and prednisone (Prednison). RESULTS Mean serum creatinine level decreased significantly after transplantation. In 6 of the 20 patients observed, 7 biopsies showed acute rejection episodes (35%). Over the 12‐month post‐transplant period, all patients showed stable graft function, with a mean serum creatinine level of 202.1 ± 130.9 μmol/L. Patient and renal graft survival rates were 100% after 12 months. Most of the observed adverse events were those commonly reported with the use of cyclosporin, and they resolved with a reduction in the cyclosporin dose. Equoral treatment demonstrated an acceptable safety profile with maintenance of satisfactory and stable renal function. CONCLUSIONS Equoral as a primary immunosuppressant for de novo kidney transplant recipients seems effective and safe in terms of acute rejection rate, patient and renal graft survival rates, and side effect profiles.

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Section: Discussionsupporting

confidence: 93%

mentioning

confidence: 73%

Efficacy of Equoral in Prophylactic Immunosuppression after De Novo Kidney Transplantation

Zadrazil¹,

Jabry²,

Horák³

et al. 2007

Dialysis & Transplantation

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“…Since then, other companies are free to manufacture interchangeable generic products. Up to now, several generic CsA formulations have been developed [24][25][26][27][28][29][30][31], and most of them have recently become available in Europe. They demonstrate bioequivalence criteria according to the current regulations [32].…”

Section: The Advent Of Novel Csa Generic Formulationsmentioning

confidence: 99%

“…Moreover, since the patient pool is not homogeneous, for critical drugs like CsA, close monitoring is required when different formulations are switched each others. Equoral (IVAX-CR, Opava, Czech Republic), is a new formulation tested as bioequivalent to CsA Neoral in 12 healthy volunteers [30] and recently confirmed as clinically bioequivalent in 15 stable renal transplant patients switched from Neoral capsules to Equoral capsules [31]. It should be pointed out, however, that bioequivalence studies should be conducted with a large number of subjects, usually 20-40 [42].…”

Section: The Advent Of Novel Csa Generic Formulationsmentioning

confidence: 99%

Generic cyclosporine formulations: more open questions than answers

Cattaneo¹,

Perico²

2005

Transplant Int

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Summary The introduction of cyclosporine (CsA) in clinical practice has significantly improved patient and allograft survival after organ transplantation. The new microemulsion CsA formulation, Neoral, has been associated with a more reproducible absorption and a better patient outcome as compared to the old formulation Sandimmune. Recently, several generic CsA formulations have been tested as bioequivalent to Neoral. Bioequivalence tests have been performed in selected groups of young, healthy male volunteers usually in single‐dose studies, and then extended to completely different population, such as transplant recipients. However, growing body of evidence shows that CsA pharmacokinetics in healthy subjects is different from that of transplant patients, treated chronically with CsA. Therefore, converting patients from Neoral to the new generic formulations could be detrimental, exposing patients to increased risk of graft function deterioration and graft loss. Thus, more research and more accurate bioequivalence tests are required to address the unanswered problems dealing with the generic CsA formulations.

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“…The primary aim of our studies was not to demonstrate bioequivalence, but we emphasize that we would have probably found bioequivalence between Neoimmun and Neoral or Neoimmun fed vs fasting using more subjects, rendering the 90% confidence interval more narrow, as the point estimates of c max as well as of AUC were between 80 and 125%. Bioequivalence between Equoral (Neoimmun) and Neoral has been reported in a previously published study in 12 healthy volunteers according to the authors' statement (Andrysek et al 2003). However, the experimental setting of the study and the test medication were not precisely described, and the result of the bioequivalence test was not provided.…”

Section: Discussionmentioning

confidence: 99%

Neoimmun versus Neoral: a bioequivalence study in healthy volunteers and influence of a fat-rich meal on the bioavailability of Neoimmun

Kees

Bucher

Schweda

et al. 2007

Naunyn-Schmied Arch Pharmacol

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In two crossover studies with 12 (6 males/6 females) healthy young volunteers each, we compared the bioavailability of Neoimmun capsules with the microemulsion Neoral and the influence of a fat-rich breakfast on the bioavailability of Neoimmun. Each volunteer received a single dose of 200 mg cyclosporine A in each period. Blood samples were taken up to 24 h and analysed for cyclosporine A by high-performance liquid chromatography (HPLC) and photometric detection. The pharmacokinetic parameters were determined by non-compartmental analysis. The treatments were tested for bioequivalence and significant differences. The bioavailability of Neoimmun was significantly lower compared to Neoral, albeit Neoimmun met the bioequivalence criterion (90% confidence interval of AUC 0.80-0.94) or missed the criterion only marginally (90% confidence interval of c max 0.75-0.91). The bioavailability of Neoimmun as determined by area under the blood concentration-time curve (AUC) increased by nearly 20% after a fat-rich breakfast. However, mean peak concentrations after food were only higher in male subjects, whereas mean peak concentrations in female subjects were lower compared to fasting administration. In conclusion, our data show that Neoimmun exhibits a lower bioavailability than the microemulsion Neoral and that food has a significant but variable and sex-dependent impact on the bioavailability of Neoimmun capsules.

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Equoral, new cyclosporine drug delivery system, versus neoral: a bioequivalence study in healthy volunteers

Cited by 15 publications

References 3 publications

Efficacy of Equoral in Prophylactic Immunosuppression after De Novo Kidney Transplantation

Efficacy of Equoral in Prophylactic Immunosuppression after De Novo Kidney Transplantation

Generic cyclosporine formulations: more open questions than answers

Neoimmun versus Neoral: a bioequivalence study in healthy volunteers and influence of a fat-rich meal on the bioavailability of Neoimmun

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