Navegando por Palavras-chave "therapeutic drug monitoring"

Agora exibindo 1 - 4 de 4
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Enteric-coated mycophenolate sodium provides higher mycophenolic acid predose levels compared with mycophenolate mofetil: Implications for therapeutic drug monitoring
    (Lippincott Williams & Wilkins, 2007-06-01) Budde, Klemens; Tedesco-Silva, Helio; Pestana, Jose Medina; Glander, Petra; Neumayer, Hans-H.; Felipe, Claudia Rosso; Machado, Paula Pinheiro; Sechaud, Romain; Schmouder, Robert; Charite Univ Med Berlin; Universidade Federal de São Paulo (UNIFESP); Novartis Pharma; Novartis Pharmaceut Corp
    The delayed release of mycophenolic acid (MPA) from enteric-coated mycopbenolate sodium (EC-MPS) may lead to different MPA predose (CO) levels compared with mycopbenolate mofetil (MMF). A post hoc analysis was performed on MPA morning predose values assessed in 88 maintenance renal transplant patients from three studies converted from MMF (1000 mg twice a day) to equimolar EC-MPS (720 mg twice a day) or vice versa, both in combination with cyclosporine. the median MPA predose level was approximately 30% higher when patients received EGMPS (2.40 mu g/mL; range, 0.49-39.30 mu g/mL) compared with MMF (1.83 mu g/mL; range, < 0.1-12.80 mu g/mL). Rare cases (3.0%) of high MPA CO levels 15 mu g/mL or greater were observed with EGMPS consistent with a very prolonged release of MPA from this formulation. Both EGMPS and MMF exhibited a poor correlation between MPA CO levels and exposure as assessed by MPA area under the curve. Physicians targeting a certain MPA predose level have to be aware of the higher morning CO levels with EGMPS, whereas the overall MPA exposure is not different to MMF.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    How Delayed Graft Function Impacts Exposure to Mycophenolic Acid in Patients After Renal Transplantation
    (Lippincott Williams & Wilkins, 2011-04-01) van Gelder, Teun; Silva, Helio Tedesco [UNIFESP]; Fijter, Hans de; Budde, Klemens; Kuypers, Dirk; Mamelok, Richard D.; Armstrong, Victor W.; Oellerich, Michael; Erasmus MC; Universidade Federal de São Paulo (UNIFESP); Leiden Univ; Charite; Leuven Univ; Mamelok Consulting; Univ Gottingen
    Introduction: Mycophenolic acid (MPA) plasma concentrations are highly variable on standard-dose mycophenolate mofetil therapy. At creatinine clearances below 25 mL/min, MPA clearance increases as a result of a higher nonprotein-bound fraction. Patients with delayed graft function (DGF) after renal transplantation are exposed to low total MPA concentrations, when risk of rejection is highest. This study investigated the influence of DGF on MPA exposure and on clinical outcome.Methods: Adult renal transplantation patients treated with mycophenolate mofetil, corticosteroids, and either microemulsified cyclosporine (n = 459) or tacrolimus (n = 371) participated in a randomized controlled trial (the Fixed-Dose Concentration-Controlled [FDCC] Study). Abbreviated MPA areas under the curve (AUCs) were obtained on Day 3, Day 10, Week 4, and Month 3, to calculate MPA AUC((0-12)). Free MPA AUC values were available for a subgroup of patients (n = 269).Results: the overall incidence of DGF was 187 of 830 (23%) and did not differ between cyclosporine-treated (24%) and tacrolimus-(21%) treated patients. the incidence of biopsy-proven acute rejection at 12 months was significantly higher in patients with DGF (13.8% versus 21.4%). Patients with DGF had significantly lower dose-corrected MPA AUC on Day 3 and Day 10. Free MPA fraction and dose-corrected free MPA AUC were significantly higher in patients with DGF, from Day 3 until Month 3. the total number of patients with at least one opportunistic infection was significantly higher in patients with DGF (33.2%) compared with patients without DGF (25.8%) (P = 0.048). Patients with DGF developing opportunistic infections did not have higher total MPA AUC nor higher free MPA AUC compared with those without opportunistic infections.Conclusion: Patients with DGF have significantly lower dose-corrected MPA AUC in the first month after renal transplantation, presumably as a result of enhanced MPA clearance on account of the elevated MPA free fraction. Because patients with DGF have a higher rate of acute rejection and lower MPA exposure, higher dosing of mycophenolate mofetil in such patients may improve outcome. However, the already increased incidence of opportunistic infections in patients with DGF is a concern.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Limited Sampling Strategies Drawn Within 3 Hours Postdose Poorly Predict Mycophenolic Acid Area-Under-the-Curve After Enteric-Coated Mycophenolate Sodium
    (Lippincott Williams & Wilkins, 2009-10-01) Winter, Brenda C. M. de; van Gelder, Teun; Mathot, Ron A. A.; Glander, Petra; Tedesco-Silva, Helio [UNIFESP]; Hilbrands, Luuk; Budde, Klemens; van Hest, Reinier M.; Erasmus Univ; Humboldt Univ; Universidade Federal de São Paulo (UNIFESP); Radboud Univ Nijmegen
    Previous studies predicted that limited sampling strategies (LSS) for estimation of mycophenolic acid (MPA) area-under-the-curve (AUC(0-12)) after ingestion of enteric-coated mycophenolate sodium (EC-MPS) using a clinically feasible sampling scheme may have poor predictive performance. Failure of LSS was thought to be due to the slow absorption of MPA causing late and variable times of maximum MPA concentration and variable predose concentrations. The aim of this study was to formally test the performance of LSS by developing and validating LSS for estimation of MPA AUC(0-12) after EC-MPS administration. Pharmacokinetic data from 109 renal transplant recipients collected during the maintenance period after transplantation were analysed retrospectively. LSS were developed separately for renal transplant patients who concurrently used cyclosporine (n = 79) and for patients not concurrently treated with cyclosporine (n = 30). Data were split into an index and a validation data set. For clinical feasibility reasons, a LSS could consist of a maximum of 3 sampling time points with the latest sample drawn 2 hours after drug administration. LSS with the latest sample drawn 3 hours after drug administration or even later were also tested. The validation of the developed LSS showed that MPA AUC(0-12) for patients concurrently treated with cyclosporine was best estimated by AUC(0-12) (mg.h.L(-1)) = 36.536 + 1.642 x C(0.5) + 0.569 x C(1.5) + 0.905 X C(2) (r(2) = 0.33, bias = -1.0 mg.h.L(-1), precision = 24 mg.h.L(-1)), whereas AUC(0-12) [mg.h.L(-1)] = 19.801 + 1.827 x C(0.5) + 1.111 x C(1) + 1.429 x C(2) was the best AUC(0-12) estimator for patients not cotreated with cyclosporine (r(2) = 0.31, bias = 0.4 mg.h.L(-1), precision = 14.5 mg.h.L(-1)). Both LSS showed poor precision and overestimation of AUC(0-12) values below the therapeutic window and underestimation of AUC(0-12) values above the therapeutic window of MPA. Using C(3) as latest sampling time point improved the fit slightly, but not satisfactory, with r(2) still <0.40 and precision still >14.0 mg.h.L(-1). Estimation of MPA AUC(0-12) with LSS for EC-MPS drawn within 2 or 3 hours postdose in renal transplant recipients in the maintenance period is likely to result in biased and imprecise results.
  • Nenhuma Miniatura disponível
    Item
    Somente Metadadados
    Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations
    (Springer, 2003-07-01) Felipe, Claudia Rosso [UNIFESP]; Tedesco-Silva, Hélio [UNIFESP]; Machado, Paula Goulart Pinheiro [UNIFESP]; Garcia, Riberto [UNIFESP]; Moreira, Silvia Regina da Silva [UNIFESP]; Medina-Pestana, José Osmar [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    This study analyzed early changes in trough blood cyclosporine concentrations and cyclosporine exposures after kidney transplantation. Seventy-two patients who received cyclosporine-based immunosuppressive therapy were intensively monitored (CO) during the first 6 months after transplantation. Full pharmacokinetic studies were performed at day 4, and months 2, 3, and 6 after transplantation. Mean steady-state, dose-adjusted trough cyclosporine blood concentrations increased from 1.1+/-0.60 (day 7) to 2.0+/-1.20 ng/ml per mg (day 30, P<0.01). Steady-state, dose-adjusted cyclosporine exposure parameters (C0, Cmax, AUC, Cavg, and C12) were significantly lower at day 4 than at months 2, 3, and 6 after transplantation (P<0.01). Initial cyclosporine doses produced target concentrations in only 30% of the patients at day 3. C2 was the single concentration that showed high and consistent correlation with serial AUC measurements (r(2)greater than or equal to0.76). the incidence of biopsy-proven acute rejection was 20.5% and was not associated with ethnicity, HLA mismatch, adjunctive therapy, or blood trough cyclosporine concentrations below 200 ng/ml at day 3. Significant time-dependent increases in steady-state cyclosporine exposure occur during the first month after kidney transplantation. Due to the low relative bioavailability early after surgery, higher doses and more frequent cyclosporine dose adjustments are necessary to produce target exposures early after transplantation.