***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: INTRODUCTION The bioequivalence of generic formulations is established by measuring pharmacokinetic parameters in healthy volunteers .  Cyclosporine ( CsA ) absorption and exposure is known to differ between healthy volunteers and transplant recipients . Therefore bioequivalence testing may be inadequate to ensure therapeutic equivalence . We sought to compare the efficacy of generic cyclosporine ( ArpimuneME , RPG Life Sciences ) versus S and immune Neoral in de novo renal transplant recipients . METHODS A prospect i ve single-center , open-label study enrolled 20 de novo renal transplant patients ( group 1 : mean age 30.55 + /- 9.81 years , M : F 19:1 , mean donor age 43.4 + /- 10.8 ) . All patients received ArpimuneME along with azathioprine and prednisolone . The results were compared with 17 matched controls ( group 2 : mean age 28.1 + /- 9.5 years , M : F 13:4 , mean donor age 47.8 + /- 6.8 ) who received Neoral and were transplanted during the same period . C(2 ) levels were monitored by the cloned enzyme donor immunoassay  ( CEDIA ) . RESULTS Patient and graft survivals were 100 % and 100 % and 100 % and 92.8 % in groups 1 and 2 , respectively ( P = NS ) . Six patients ( 30 % ) experienced rejection in group 1 as compared eight patients ( 47.1 % ) in group 2 . Mean CsA levels ( ng/mL ) during the first month were 1419.1 + /- 213.6 and 1460.5 + /- 290.7 and at 3 months , 1296.3 + /- 227.8 and 1342.4 + /- 303.4 in the two groups , respectively ( P = NS ) . The mean serum creatinine levels ( mg% ) in group 1 and group 2 were 1.6 + /- 0.8 and 2.0 + /- 1.4 at discharge and 1.5 + /- 0.4 and 1.5 + /- 0.8 at 6 months , respectively ( P = NS ) . CONCLUSION Use of a generic microemulsion form of CsA provided safe and effective immunosuppression compared with S and immune Neoral when drug monitoring was performed by C(2 ) levels BACKGROUND There is a growing concern about the therapeutic equivalence of the generic tacrolimus formulation ( GEN Tacrolimus ) to the reference tacrolimus ( REF Tacrolimus ) in solid organ transplantation . METHODS A prospect i ve , r and omized study of 126 de novo renal transplant patients was conducted to compare the efficacy , safety and pharmacokinetic ( PK ) profiles between GEN tacrolimus ( n = 63 ) and REF tacrolimus ( n = 63 ) . The PK of tacrolimus was evaluated on Day 10 and 6 months under steady-state condition . Crossover study was carried out in 66 patients at 6 months . RESULTS On Day 10 , 117 patients completed PK profiles ( 54 GEN tacrolimus and 63 REF tacrolimus ) and GEN tacrolimus showed comparable C(0 ) ( 9.8 ± 2.5 versus 9.7 ± 3.0 ng/mL , P = 0.80 ) but significantly higher dose-normalized C(max ) ( 309.1 ± 191.9 versus 192.5 ± 95.2 ng/mL/mg/kg , P < 0.001 ) . The dose-normalized AUC(0 - 12 ) tended to be higher in the GEN tacrolimus than in the REF tacrolimus group ( 1513.4 ± 935.4 versus 1262.5 ± 593.5 ng.h/mL/mg/kg , P = 0.084 ) . Because of this early and high C(max ) with a rapid decline in GEN tacrolimus concentration , the trough concentration was maintained lower than that of REF tacrolimus . At 6 months , GEN tacrolimus showed equivalent dose-normalized AUC(0 - 12 ) ( 1882.2 ± 935.6 versus 1718.1 ± 946.3 ng.h/mL/mg/kg , P = 0.429 ) but still higher dose-normalized C(max ) ( 346.3 ± 184.4 versus 273.2 ± 148.9 ng/mL/mg/kg , P = 0.056 ) , despite a reduced trough concentration ( 5.7 ± 1.6 versus 6.9 ± 2.2 ng/mL , P = 0.004 ) . PK profiles evaluated at 9 months showed that generic substitution also result ed in an ' early and high C(max ) ' . Efficacy and safety data were comparable over the 9-month study period . CONCLUSIONS Therapeutic equivalence and the PK of GEN tacrolimus should be evaluated in patients undergoing de novo renal transplantation OBJECTIVE Our objective was to evaluate the safety , efficacy , and need for dosage adjustments when patients taking the Neoral formulation of cyclosporine  are converted to the  generic formulation  , Gengraf . METHODS From September 2001 through January 2002 , patients receiving follow-up care in the renal transplant clinic at the VA Tennessee Valley Healthcare System were converted from Neoral to Gengraf based on a 1:1 dosing equivalency . Steady-state cyclosporine trough concentrations were obtained both prior to and following Neoral-to-Gengraf conversions . Patients were also monitored for changes in serum creatinine , hospitalization , cyclosporine toxicity , graft rejection , and need for further adjustment in cyclosporine regimen . RESULTS Forty-one patients were included in data analysis . There were no differences in cyclosporine concentrations ( P = .0853 ) or serum creatinine ( P = .4469 ) following conversion to Gengraf . There were no reports of cyclosporine toxicity , no episodes of graft rejection , and no need for further dose adjustment related to the generic conversion . CONCLUSIONS Neoral and Gengraf are therapeutically equivalent cyclosporine formulations , such that renal transplant recipients maintained on Neoral can be safely and effectively converted to the Gengraf formulation based on a 1:1 conversion ratio . The use of Gengraf over Neoral within the Veterans Affairs Healthcare System offers a reduced cost alternative but maintains equal efficacy and outcomes Cyclosporine A ( CyA ) is a st and ard component of immunosuppressive regimen after heart transplantation in most centres . The widespread clinical use of cyclosporine-based immunosuppressive regimens since 1983 has led to significant improvements in the survival of cardiac allograft recipients due to decreased mortality from infections and rejections . ( 1 - 3 ) CyA has been shown to be safe and effective . Owing to its success when used after the heart transplantation the number of patients has also risen . This caused growing financial dem and s on health insurance companies in the Czech Republic where the immunosuppressive drugs are fully reimbursed . A prospect i ve r and omized study in 11 stable heart transplant patients was performed to compare the efficacy and safety of  Consupren ( IVAX-CR ) a S and immun Neoral ( Novartis ) solution based immunosuppressive regimen .  The results suggest that Consupren solution  can be used as an alternative treatment to S and  immun Neoral  in CyA based regimen Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more Neoral was replaced with a generic cyclosporine formulation on our hospital formulary . We compared outcomes for de novo kidney transplant recipients who either received Gengraf ( n=88 ) or Neoral ( n=100 ) in a single-center , retrospective review . As compared to patients who received Neoral , patients who received Gengraf were significantly more likely to have an acute rejection episode ( 39 % vs. 25 % , P=0.04 ) , more likely to have a second rejection episode ( 13 % vs. 4 % ; P=0.03 ) , or to have received an antibody preparation to treat acute rejection ( 19 % vs. 8 % ; P=0.02 ) . Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by % CV ( P<0.05 ) . The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral . A larger , prospect i ve analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients OBJECTIVES Iminoral is the generic microemulsion of cyclosporine . We performed a r and omized double-blind multicenter trial to evaluate its efficacy and safety compared with the innovator medication Neoral for preventing acute rejection episodes in adult patients during the first year after renal transplant . MATERIAL S AND METHODS We used 221 de novo renal transplant recipients from 6 transplant centers in Iran enrolled between April 2008 , and January 2010 . They were r and omized to receive either Iminoral or Neoral as the calcineurin inhibitor component of the immunosuppressive regimen in addition to mycophenolate mofetil and oral corticosteroids . They were followed-up for 1 year . The primary endpoint was the rate of acute allograft rejection . Secondary endpoints consisted of 1-year graft survival rates , daily dosages of cyclosporine , trough and C2 cyclosporine blood level , serum creatinine levels , patient death rates , discontinuing the study drug , tolerability , and adverse events . RESULTS The risk of acute rejection episode during the first month after transplant was 9 % for Iminoral and 10 % for Neoral ; these declined to 4 % and 2 % during next 11 months . One-year graft survival rate was 0.86 for both groups . Renal function stabilized during the first month . Declination of the creatinine levels was similar between the 2 groups and reached a stable value of 114.9 μmol/L five months after the transplant . The frequency of clinical complications was similar between the groups . CONCLUSIONS Iminoral is safe and effective when used in de novo kidney transplant patients as an immunosuppressive medication PURPOSE The patent covering mycophenolate mofetil ( MMF ) in Korea has expired and , thus , several generic MMF agents are now commercially available . The supply of Cellcept ( Roche Korea ) was interrupted at the end of 2011 , so it was inevitable that a generic MMF would be used instead . During this period , we performed a prospect i ve pilot study to examine the safety and efficacy of a generic mycophenolate agent ( Myconol : Hanmi Pharmaceutical , Seoul Korea ) for use as conversion maintenance therapy in stable liver transplantation ( OLT ) recipients . METHODS OLT recipients , who were treated with MMF on an outpatient basis from January 2012 to March 2012 , attended follow-up interviews conducted . The patients had undergone OLT ≥ 2 years before the study , had tolerated Cellcept , and showed stable liver function . Fifty-three patients were followed up for more than 3 months after conversion to the same dose of Myconol . RESULTS After conversion to Myconol , 6 patients ( 11.3 % ) experienced new side effects , which disappeared when they reverted to Cellcept ( n = 5 ) or stopped taking Myconol medication ( n = 1 ) . The side effects associated with Myconol  included gastrointestinal symptoms ( indigestion and diarrhea ; n = 3 ) , skin eruptions ( n = 1 ) , pruritus ( n = 1 ) , and insomnia ( n = 1 ) . The mean mycophenolic acid levels were 1.71 ± 0.88 μg/mL for Cellcept and 1.83 ± 0.91 μg/mL for Myconol , which showed a strong correlation ( r(2 ) = 0.92 , P < .001 ) . CONCLUSIONS Myconol showed similar pharmacokinetics to those of Celcept , but a small proportion of patients experienced agent-specific side effects ; therefore , patients should be closely monitored when taking Myconol . Also , further studies , with a greater number of patients , are required to identify the full spectrum of drug-associated side effects Background . Gengraf capsule , an AB-rated generic cyclosporine for Neoral , has been shown to be bioequivalent in previous studies . The purpose of this pharmacokinetic study performed in stable renal transplant recipients was to evaluate interchangeability of Gengraf and Neoral . Methods . Using an open-label , three-period design , 50 renal transplant recipients taking stable doses of Neoral completed a multicenter study . Subjects continued their Neoral regimen during period I ( days 1–14 ) . Subjects then switched from Neoral on a milligram-for-milligram basis to Gengraf during period II ( days 15–28 ) , followed by conversion to the same milligram-for-milligram dosing regimen of Neoral during period III ( days 29–35 
    Output:
    
Acute rejection was rare but did not differ between groups .