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Web-Based Registry for Cytomegalovirus (CMV) Infection and Disease after Pediatric Renal Transplantation.
No full textWeb-based registry for cytomegalovirus (CMV) infection and disease after pediatric renal transplantation.
No full textWeb-Based Registry for Cytomegalovirus (CMV) Infection and Disease after Pediatric Renal Transplantation - Intermediate Analysis.
No full textWeb-Based Registry for Cytomegalovirus (CMV) Infection and Disease after Pediatric Renal Transplantation.
No full textWeb-Based Registry for Cytomegalovirus (CMV) Infection and Disease after Pediatric Renal Transplantation - Intermediate Analysis.
No full textValidation of an abbreviated pharmacokinetic profile for the estimation of mycophenolic acid exposure in pediatric renal transplant recipients
No full textThe pharmacokinetics of mycophenolic acid (MPA), the active moiety of the immunosuppressant mycophenolate mofetil (MMF), exhibits large inter-individual variability. Concentration-controlled dosing of MMF based on therapeutic drug monitoring may therefore be advantageous compared to a fixed-dose regimen. Because full AUC(0-12) monitoring is not practical and predose MPA concentrations correlate only moderately with the corresponding AUC(0-12), the estimation of MPA exposure by a limited sampling strategy has been suggested. However, before such an algorithm is transferred to clinical practice, it is compulsory to prospectively validate it in a different data set, in order to avoid biased results. The aim of this investigation was therefore to prospectively validate an algorithm based on an abbreviated pharmacokinetic (RK) profile for the estimation of MPA exposure in 54 pediatric renal transplant recipients (169 PK profiles) on MMF in conjunction with CsA and prednisone on a second data set in a different group of patients with a similar immunosuppressive regimen (25 patients, 119 PK profiles). An algorithm based on three PK sampling timepoints during the first 2 hours after MMF dosing (estimated AUC(0-12) = 18.6 + 4.3 center dot C-0 + 0.54 center dot C-0.5 + 2.15 center dot C-2) was able to predict the corresponding MPA-AUC(0-12) with a low percentage prediction error (10.7%) and an acceptable coefficient of determination (r(2) = 0.76). The performance of this algorithm was comparable among different pediatric age groups. By ROC curve analysis, the calculated MPA-AUC(0-12) based on this algorithm was able to differentiate between rejecters and non-rejecters with a comparable prognostic sensitivity (66.7%) and specificity (61.9%) as the full-time MPA-AUC(0-12). In conclusion, the use of this validated algorithm for the estimation of MPA exposure based on a limited sampling strategy during the first 2 hours after MMF dosing has the potential to optimize MMF therapy in pediatric renal transplant recipients
Long-term pharmacokinetics of mycophenolic acid in pediatric renal transplant recipients over 3 years posttransplant
No full textData on exposure to mycophenolic acid (MPA), the active moiety of mycophenolate mofetil (MMF), in pediatric renal transplant recipients beyond the first year posttransplant are scarce. The authors therefore analyzed the long-term pharmacokinetics of MPA in 25 pediatric patients treated with 600 mg MMF/m(2) body surface area twice a day in conjunction with cyclosporine A and prednisone. Plasma samples for 12-hour pharmacokinetic profiles were collected on day 7, and after 3, 9, 24, and 36 months posttransplant. Both the actual and the dose-normalized MPA-area under the concentration-time curve (AUC(0-12)) increased approximately 2-fold between day 7 and month 9 but stabilized thereafter. Both the actual and the dose-normalized MPA-AUC(0-12) at months 24 and 36 were comparable to that at month 9. Presuming a therapeutic window of 30-60 mg h/L, 15 (60%) of 25 patients at day 7 had an MPA-AUC(0-12) < 30 mg h/L, indicating potential underexposure, whereas the proportion of patients with an MPA-AUC(0-12) <30 mg h/L between months 3 and 36 was low (5%-17%). These data suggest that the recommended MMF dose of 600 mg/m(2) body surface area twice a day in conjunction with cyclosporine A leads to MPA underexposure early posttransplant in a significant subset of patients, indicating a need for a higher initial MMF dose. Dose-normalized MPA exposure increases in the first 9 months posttransplant, consistent with a reduced MPA metabolism and increased enterohepatic recycling of MPA
Consequences of CYP3A4 and MDR-1 polymorphisms on pharmakokinetic parameters of cyclosporin a and mycophenolic acid in pediatric renal transplant recipients.
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Inosine 5 '-Monophosphate Dehydrogenase (IMPDH) Activity in Children and Adolescents: Physiological Regulation and Response to Mycophenolic Acid (MPA) Therapy.
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