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Objective To investigate the exposure difference of different dosage forms of mycophenolic acid (MPA) between children aged ≤12 and > 12 years old after kidney transplantation. Methods Clinical data of 73 children undergoing kidney transplantation from donation after cardiac death (DCD) were retrospectively analyzed. Postoperative immunosuppressive regimen was MPA+ tacrolimus+glucocorticoid. According to different dosage forms of MPA, all recipients were divided into group A (n=37, mycophenolate mofetil capsules), group B (n=28, enteric-coated mycophenolate sodium) and group C (n=8, mycophenolate mofetil dispersible tablets). All children were divided into ≤12 and > 12 years old groups according to the age of kidney transplantation. The daily dosage of different dosage forms was calculated. The blood concentration (C) of MPA and the area under the curve (AUC) were detected by enzyme-multiplied immunoassay technique. The MPA blood concentration was statistically compared between two age groups at different time points. The recovery of renal function and postoperative complications were assessed. Results No significant differences were observed in the dosage and blood concentration of drug at different time points among groups A, B and C (all P > 0.05). The MPA-C4 h and AUC in the ≤12 years old group were significantly higher than those in the > 12 years old group (both P < 0.05). In group B, the MPA-C4 h of children aged ≤12 years old was significantly higher compared with that in those aged > 12 years old (P=0.016). The MPA-C4 h of children aged ≤12 years old in group B was higher than those in group A and group C, but the differences were not statistically significant (P=0.080). There was no significant difference in the incidence of acute rejection and infection among three groups (both P > 0.05). Conclusions Children of different ages who are given with different dosage forms of MPA after kidney transplantation obtain different exposure rates. The exposure rate of kidney transplant recipients aged ≤12 years old tends to be higher than that of their counterparts aged > 12 years old, mainly seen in the recipients treated with enteric-coated mycophenolate sodium. Therefore, it is necessary to monitor the exposure level of MPA, which provides significant guidance for adjusting the drug dosage of different dosage forms.
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<p><b>Background</b>Immunosuppressive agents are still inefficient in preventing biopsy-proven acute rejection (BPAR) after expanded criteria donor (ECD) kidney transplantation. The aim of this study was to investigate the relationships between early immunosuppressive exposure and the development of BPAR.</p><p><b>Methods</b>We performed a retrospective study of 58 recipients of ECD kidney transplantation treated with enteric-coated-mycophenolate sodium, tacrolimus (Tac), and prednisone. The levels of mycophenolic acid-area under the curve (MPA-AUC) and Tac Cwere measured at the 1 week and the 1 month posttransplant, respectively. The correlation was assessed by multivariate logistic regression.</p><p><b>Results</b>The occurrence rates of BPAR and antibody-mediated rejection were 24.1% and 10.3%, respectively. A low level of MPA-AUC at the 1 week posttransplant was found in BPAR recipients (38.42 ± 8.37 vs. 50.64 ± 13.22, P < 0.01). In addition, the incidence of BPAR was significantly high (P < 0.05) when the MPA-AUClevel was <30 mg·h·L at the 1 week (15.0% vs. 44.4%) or the Tac Cwas <4 ng/ml at the 1 month posttransplant (33.3% vs. 21.6%). Multivariable logistic regression analysis showed that the MPA-AUC at the 1 week (OR: 0.842, 95% CI: 0.784-0.903) and the Tac Cat the 1 month (OR: 0.904, 95% CI: 0.822-0.986) had significant inverse correlation with BPAR (P < 0.05).</p><p><b>Conclusions</b>Low-level exposure of MPA and Tac Cin the early weeks posttransplant reflects an increased acute rejection risk, which suggested that MPA-AUC <30 mg·h·L and Tac C <4 ng/ml should be avoided in the first few weeks after transplantation.</p>
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Graft Rejection , Allergy and Immunology , Immunosuppressive Agents , Chemistry , Therapeutic Uses , Kidney Transplantation , Methods , Mycophenolic Acid , Chemistry , Therapeutic Uses , Retrospective Studies , Tacrolimus , Chemistry , Therapeutic Uses , Time FactorsABSTRACT
PURPOSE: The increased tolerability of enteric-coated mycophenolate sodium (EC-MPS), compared to mycophenolate mofetil, among kidney transplant recipients has the potential to facilitate cyclosporine (CsA) minimization. Therefore, a prospective trial to determine the optimum EC-MPS dose in CsA-based immunosuppression regimens is necessary. MATERIALS AND METHODS: A comparative, parallel, randomized, open-label study was performed for 140 patients from four centers to compare the efficacy and tolerability of low dose CsA with standard dose EC-MPS (the investigational group) versus standard dose CsA with low dose EC-MPS (the control group) for six months in de novo kidney transplant recipients. Graft function, the incidence of efficacy failure [biopsy-confirmed acute rejection (BCAR), death, graft loss, loss to follow-up], and adverse events were compared. RESULTS: The mean estimated glomerular filtration rate (eGFR) of the investigational group at six months post-transplantation was non-inferior to that of the control group (confidence interval between 57.3 mL/min/1.73m² and 67.4 mL/min/1.73 m², p0.05) in the incidence of discontinuations and serious adverse events (SAE) between the groups. CONCLUSION: CsA minimization using a standard dose of EC-MPS kept the incidence of acute rejection and additional risks as low as conventional immunosuppression and provided therapeutic equivalence in terms of renal graft function and safety issues.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Cyclosporine/administration & dosage , Graft Rejection/prevention & control , Immunosuppressive Agents/administration & dosage , Incidence , Kidney Transplantation , Mycophenolic Acid/administration & dosage , Prospective Studies , Tablets, Enteric-Coated , Time FactorsABSTRACT
Objective:To investigate the pharmacokinetics of mycophenolic acid( MPA)and its metabolites in different stages af-ter the administration of enteric-coated mycophenolate sodium( EC-MPS)tablets in Chinese liver transplant recipients. Methods:The blood samples of 24 patients were collected in 0-12h of the 1st and 3rd week after the administration of EC-MPS. The concentrations of MPA,AcMPAG and MPAG in plasma were measured by LC-MS/MS developed in our lab. The pharmacokinetic parameters of MPA and its metabolites were estimated by non-compartmental method. Results:After 1-and 3-week therapy with EC-MPS,Cmax ,AUC0-12 and t1/2 was(18. 1 ± 8. 75)and(20. 7 ± 16. 0)μg ml-1 ,(42. 7 ± 17. 5)and(47. 1 ± 23. 9)μg·h·ml-1 ,(3. 33 ± 2. 81)and (3.30 ±1.89)h for MPA;(2.50 ±1.86)and(1.78 ±1.72)μg·ml-1,(14.5 ±11.7)and(6.97 ±6.57)μg·h·ml-1, (4. 48 ± 2. 53)and(3. 76 ± 1. 8)h for AcMPAG;(171. 6 ± 135. 4)and(152. 2 ± 115. 9)μg·ml-1 ,(1299 ± 1 204)and(1 051 ± 561)μg·h·ml-1 ,(8. 73 ± 4. 25)and(7. 75 ± 2. 87)h for MPAG,respectively. There was no significant difference in the PK parameters of MPA after the 1-and 3-week therapy. The Cmax ,Tmax and t1/2 of MPA in the patients received EC-MPS were significantly higher than those in the patients received MMF(P<0. 05). Cmax and AUC0-12 of MPAG in the patients received EC-MPS were signifi-cantly higher than those in the patients received MMF after the 3-week therapy(P<0. 05). Conclusion:There is no significant accu-mulation of MPA after the therapy with EC-MPS at different stages. The absorption of MPA is delayed after the therapy with EC-MPS compared with that with MMF. There is no difference in MPA exposure between EC-MPS and MMF in Chinese liver transplant patients.
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Objective To evaluate the effect of conversion from mycophenolat mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) on gastrointestine-related quality of life,as well as the safety and efficacy.Method A total of 41 renal transplant (RT) recipients were converted from MMF to EC-MPS (46.3 ± 17.1) months after the operation due to the gastrointestinal side effects of MMF,with a mean time of 46.3 months.Before the conversion and 12 weeks later,the patients were evaluated with Gastrointestinal Quality of Life Index (GIQLI) questionnaire,and the safety and efficacy were assessed.Result The average dose of MMF was 846.7 ± 291.3 mg/day before the conversion,with a mean dose of 639.5 ± 186.4 mg/day for EC-MPS.The total score of GIQLI was 103.6 ± 10.7 before the conversion,and 12 weeks after conversion 118.3 ± 15.1,with a statistical significance (P＜0.05).The safety of EC-MPS was excellent without infection,acute rejection episode,loss of allograft or death.The serum creatine was 136.9 ± 35.7 mol/L before conversion and 128.4± 40.8 mol/L after conversion (P ＞ 0.05).Conclusion For the RT patients with gastrointestinal side effects of MMF,conversion to EC-MPS could significantly alleviate gastrointestinal illness,and improve quality of life,with excellent safety and efficacy.
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OBJECTIVE: To determine the steady state pharmacokinetics of mycophenolic acid (MPA), the active metabolite, after an oral administration of enteric-coated mycophenolate sodium (EC-MPS) in the renal transplant patients.
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It is reported that a conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) relieves gastrointestinal (GI) symptom burden and improves health-related quality of life (HRQoL). However, it is unclear whether renal transplant recipients using tacrolimus receive the same benefit from the conversion. In this prospective, multi-center, open-label trial, patients were categorized into two groups by their GI symptom screening. Equimolar EC-MPS (n=175) was prescribed for patients with GI burdens; those with no complaints remained on MMF (n=83). Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI) were evaluated at baseline and after one month. Patients and physicians completed Overall Treatment Effect (OTE) at one month. EC-MPS-converted patients had worse GSRS and GIQLI scores at baseline than MMF-continued patients (all P<0.001). Significant improvements in GSRS and GIQLI scores were observed for EC-MPS-converted patients at one month, but MMF-continued patients showed worsened GSRS scores (all P<0.05). OTE scale indicated that EC-MPS patients improved in overall GI symptoms and HRQoL more than MMF patients did (P<0.001). In tacrolimus-treated renal transplant recipients with GI burdens, a conversion from MMF to EC-MPS improves GI-related symptoms and HRQoL.