The Assessment of the Method of Monitoring in Liver Transplant Recipients Treated with Microemulsion Cyclosporine (Neoral(R)) and Mycophenolate Mofetil (CellCept(R)) / 대한이식학회지

PURPOSE: Cyclosporine (CsA) dosing is traditionally based on trough levels (C0) rather than area under the concentration- time curve (AUC), although AUC correlates better with post- transplantation acute rejection and toxicity. It was reported that C2 (2-hour post-dose blood level) is an accurate single- sample marker for AUC0-4 in patients receiving CsA. No trials of C2 monitoring have been carried out in liver transplant recipients who are immunosuppressed with the combination of CsA and Mycophenolate Mofetil (MMF). The purpose of this study was to evaluate the correlation between C0, 1, 2, 3, 4 levels and AUC0-4 and define recommended target C2 in liver transplant recipients who are treated with CsA and MMF. METHODS: Thirty adult living donor liver transplant recipients were followed up 12 weeks after transplantation. CsA and MMF were administered in all recipients. CsA dose was reduced to the half level of target C0 in recipients treated solely with CsA. C0 and C2 were measured during in-patient period post-transplant. RESULTS: The best correlation between CsA concentration at various time points and the AUC0-4 was found at C2 (r2=0.931) (P<0.05). Mean C2 was 543.2+/-260.1 ng/mL (mean+/-SD). We observed complications associated with the immunosuppressants in six patients (20%). But, only one patient experienced acute rejection proven by biopsy and, there is no the graft loss and nephrotoxicity. CONCLUSION: In early post-transplant days, AUC0-4 was strongly correlated with C2. Reduced CsA dosing can be attempted in recipients who are immunosuppressed with the combination of CsA and MMF. The optimal target C2 probably can be suggested as about 543.2+/-260.1 ng/mL (mean+/-SD). During the in-patient period, C0 matched with target C2 can be decided. Target C0 can be individualized because C0 matched with target C2 differs in each recipients and C2 can't be checked routinely during the out-patient period.

Pharmacokinetics of Cyclosporine A and Its Therapeutic Effect in Children with Renal Diseases / 소아과

PURPOSE: To know the body handling properties and anti-proteinuric effect of cyclosporine A(CsA) in children with renal diseases, 34 patients with nephrotic syndrome or glomerular diseases were included to treatment trials and evaluated. METHODS: Microemulsion formula CsA, 5 mg/kg/day was administered orally in two divided doses for 9.3+/-4.6 months. Pharmacokinetic studies of CsA were done twice at beginning and closing of 12 months' CsA therapy. RESULTS: The steady state CsA pharmacokinetic parameters of 34 patients were as follows; Tmax:1.64+/-0.84 hr, Cmax:788+/-354 ng/dL, C12:58.7+/-33.2 ng/mL, Cavg:246+/-96 ng/mL, AUC:2,949+/-1,156 ng hr/mL, Vd:4.03+/-0.45 L/kg, CL:9.69+/-2.27 L/hr, T1/2:5.31+/-2.37 hr. C2 was the best to predict the CsA AUC(R=0.896, P<0.001). Body surface area based dosage(mg/m2/d) correlates best with AUC. Intra-individual CsA pharmacokinetic changes were not found after 12 months' therapy. Anti-proteinuric effect of CsA was considerable; 88.9% of primary nephrotic syndrome and 62.5% of secondary glomerular diseases was responsive to CsA thearpy. There was no serious complication and CsA treatment was well tolerated by the pediatric patients. CONCLUSION: CsA therapy for difficult renal diseases with proteinuria was effective and safe. For better AUC prediction of CsA, body surface area based dosage(mg/m2/d) and C2 monitoring are recommended in children with renal diseases.

Validity of C2 Monitoring of Microemulsion Cyclosporine in Early Renal Transplant Period / 대한이식학회지

PURPOSE: Four-hour area under the concentration-time curve (AUC0-4) was considered to be superior rather than C0 in predicting the development of acute rejection, and was reported most well correlated with C2 in post-transplant period. The purpose of this study was to demonstrate the correlation between AUC0-4 and each C0,1,2,3,4, and to compare C2 with C0 in predicting acute rejection in de-novo kidney recipients. METHODS: Fifty- six adult living donor kidney transplants were followed up 3 months after transplantation. Cyclosporine A (CsA) dose was adjusted with C0. AUC0-4 was measured on 5th and 19th post-operative day, and C2 as well as C0 was measured on post-operative 5, 12, 19, 30, 60, 90 days. RESULTS: Fifteen patients (26.8%) experienced acute rejection 12.0+/-10.9 (5~48) days after transplantation. CsA absorption pharmacokinetics was different with data based on Caucasian recipients. In more than 60% of patients, peak concentration (Cmax) was reached 2 hours after oral intake of CsA regardless the occurrence of acute rejection and postoperative days. AUC0-4 was most critically correlated with C2 on 5th and 19th post-operative days (R2>0.800, respectively). Recipients having acute rejection between 5th and 7th post-operative day, had statistically lowered AUC0-4, C2, C3 (P<0.05) compared with patients without acute rejection. CONCLUSION: In early post-transplant days, AUC0-4 was powerfully correlated with C2. Monitoring of C2 rather than C0 could predict the occurrence of acute rejection in this period. Value of C2 monitoring in Koreans beyond 7th day awaits further study by adjusting CsA dose with C2 rather than C0.