Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant recipients with gastrointestinal tract disorders

OBJECTIVE: The objective of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in renal transplant recipients with gastrointestinal tract (GI) reverse effects using patient-reported outcomes instrument. METHODS: A multicenter, open-label, prospective study was undertaken in renal transplant recipients treated with MMF. In patients experiencing GI tract symptoms, treatment was changed to equimolar EC-MPS (myfortic). At baseline and visit 2 (4-6 weeks after baseline), patients completed the Gastrointestinal Symptom Rating Scale (GSRS) and Gastrointestinal Quality of Life Index (GIQLI), and physicians completed the Overall Treatment Effect (OTE) scale at visit 2. A difference of 0.5 or greater in the OTE score is indicative of clinical relevance. RESULTS: Of 154 patients screened, 118 fulfilled the inclusion or exclusion criteria. Eighty-five men and 33 women with a mean age of 41.6 years participated in this study. Median time since transplantation was 12 months. Mean (SD) dose of MMF reported at baseline was 1209.4 (422.89) mg/d. More than 50% of patients reported MMF-associated nausea, dyspepsia, and abdominal pain. After conversion to an equimolar dose of EC-MPS, patients showed improvement in GI symptoms. This benefit was predominantly observed in patients with moderate to severe symptoms at baseline. On the GSRS, patients reported a significant (P < .05) reduction in symptom burden across all parameters (reflux, 36%; diarrhea, 38%; indigestion, 36%; constipation, 28%; and abdominal pain, 40%). On the GIQLI also, significant (P < .05) improvement was reported (symptoms, 18%; emotional status, 22%; physical functioning, 21%, and use of medical treatment, 18%). On the OTE scale, 84.7% of patients reported improvement in GI symptoms. CONCLUSION: In patients with moderate to severe GI symptoms, changing treatment from MMF to EC-MPS significantly reduces GI-related symptom burden and improves GI-specific quality of life.     

Improvement of gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients

As many as 50% of liver transplant patients suffer gastrointestinal (GI) disturbances post-transplant. Conversion from mycophenolate mofetil (MMF) to mycophenolate sodium (EC-MPS) alleviates GI symptom burden in renal transplant recipients. We employed a validated patient and physician-reported assessment to evaluate the impact of conversion to EC-MPS in liver transplant patients. This is a prospective, longitudinal, single-center, open-label pilot study. Thirty-one MMF-treated liver transplant patients with GI symptoms were converted to equimolar EC-MPS. Gastrointestinal Symptom Rating Scale (GSRS), GI Quality of Life, SF-12v2 and physician-reported assessments were used to evaluate GI symptom burden and severity. A significant improvement in overall GSRS score was noted from baseline (2.57; 95% CI 2.12-3.10) to one month (1.90; 1.68-2.12; p = 0.0007) and three months (1.82; 1.60-2.04; p = 0.0002) post-conversion with significant reductions in all subgroups except Reflux. The overall Gastrointestinal Quality of Life Index (GIQLI) score also showed significant increase in health-related quality of life between one month (90.89; 84.04-97.75) and three months (100.04; 94.57-105.51; p = 0.0009), with all subgroups except social functioning (p = 0.0861) and medical treatment (p = 0.3156) demonstrating significant improvements. This pilot study demonstrates improvement in GI symptom burden when converting from equimolar doses of MMF to EC-MPS. This benefit persisted for three months without evidence of rejection.     

Renal transplant patients with gastrointestinal intolerability to mycophenolate mofetil: conversion to enteric-coated mycophenolate sodium

The introduction of mycophenolate mofetil (MMF) was an important advance in immunosuppressive therapy, although its use is limited by adverse gastrointestinal events. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed to avoid these side effects. Recent clinical trials have demonstrated that EC-MPS is a safe drug in both de novo and maintenance renal transplant patients. In this prospective study, therapeutically equivalent doses of EC-MPS were administered to 39 stable kidney transplant patients receiving MMF. After 3 months of treatment with EC-MPS the incidence of adverse gastrointestinal events was lower (15.8% of the patients). There were higher levels of mycophenolic acid after conversion to EC-MPS, probably due to better absorption. These factors allowed decreased doses and levels of calcineurin inhibitors without increasing the risk of graft rejection. At 3 months postconversion, serum creatinine improved from the mean baseline value of 1.83 +/- 0.12 mg/dL to 1.70 +/- 0.10 mg/dL. In conclusion, EC-MPS was well tolerated in maintenance renal transplant patients with adverse gastrointestinal events secondary to MMF.     

Improvement in 3-month patient-reported gastrointestinal symptoms after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in renal transplant patients

BACKGROUND: The benefit of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in terms of gastrointestinal symptom burden has been evaluated previously using patient-reported outcomes. However, data are lacking concerning the sustained effect of conversion over time, and the potential impact of concomitant calcineurin inhibitor. METHODS: In this 3-month, prospective, multicenter, longitudinal, open-label trial, MMF-treated renal transplant patients with gastrointestinal symptoms receiving cyclosporine or tacrolimus were converted to equimolar doses of EC-MPS. Change in gastrointestinal symptom burden was evaluated using a validated Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: A significant improvement in GSRS score was observed from baseline (2.61, 95% CI 2.54-2.68) to month 1 (1.87, 95% CI 1.81-1.93) after conversion to EC-MPS and was sustained to month 3 (1.81, 95% CI 1.74-188; both P<0.0001 versus baseline). The mean change in overall GSRS score from baseline to month 1 was -0.74 overall (cyclosporine: -0.73 and tacrolimus: -0.74; all P<0.0001 versus baseline), with a slight further improvement (-0.79) at month 3 (cyclosporine: -0.82 and tacrolimus: -0.78; all P<0.0001 versus baseline). A significant improvement in GSRS subscale scores was also observed in the total population regardless of calcineurin inhibitor at month 1, sustained to month 3 (all P<0.0001 versus baseline). The improvement in GSRS score postconversion was similar in African-American and non-African-American patients, and in diabetic and nondiabetic patients. CONCLUSIONS: This exploratory study in 728 patients demonstrates that following conversion from MMF to EC-MPS, regardless of concomitant calcineurin inhibitor, GSRS is improved and sustained over 3 months.     

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable maintenance renal transplant patients: pooled results from three international, multicenter studies

BACKGROUND: Mycophenolate mofetil (MMF) is effective in renal transplant patients but concerns remain over its gastrointestinal (GI) tolerability. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) has been developed with the intention of improving mycophenolic acid-related GI tolerability. METHODS: Data were pooled in a planned analysis of three subprotocols of the myfortic Prospective Multicenter Study (myPROMS). In a 6-month study, efficacy and safety of converting stable renal transplant recipients from MMF to a bioequivalent dose of EC-MPS for mycophenolic acid exposure were evaluated. Treatment efficacy was recorded and graft function was assessed by measuring serum creatinine and estimating creatinine clearance. Adverse events (AEs) and infections were monitored and the incidence of EC-MPS dose changes was recorded. RESULTS: A total of 588 patients were recruited, 564 (96%) of whom completed the study. The rate of treatment failure (defined as biopsy-proven acute rejection, graft loss, or death) was 1.9%, with no episodes of graft loss and only one death reported during the study. Renal function remained stable throughout the trial. EC-MPS was well tolerated; the majority of AEs were mild or moderate in severity. Dose reductions or interruptions were required by 6.3% and 1.9% of patients, respectively. Gastrointestinal AEs occurred in 138 patients (23.5%). The rate of dose adjustment as a result of a GI AE was 2.2%. CONCLUSIONS: Equimolar conversion from MMF to EC-MPS in maintenance renal transplant patients was safe and maintained efficacy.     

Questionnaire-based evaluation of gastrointestinal disorders in de novo renal-transplant patients receiving either mycophenolate mofetil or enteric-coated mycophenolate sodium.

BACKGROUND: Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of our prospective questionnaire-based study was to assess GI side-effects in de novo renal-transplant patients receiving either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS). METHODS: Between January 2002 and April 2003, all patients receiving MPA with a functioning allograft at 1 month post-transplantation were enrolled in this study (n = 130). Ninety-three of them received MMF (group I), and 37 patients received EC-MPS (group II). Each month, every patient completed a questionnaire regarding GI disorders. RESULTS: During the first year post-transplantation, GI disorders occurred in 31 patients from the MMF group (33.3%) and 12 patients from the EC-MPS group (32.4%) (not significant). The incidence of upper GI disorders was also similar in both groups. Diarrhoea was observed in 18 patients (19.3%) from group I, and in five patients from group II (13.5%) (not significant). Its frequency and severity were similar in both groups. Weight loss was observed in three patients receiving MMF. Diarrhoea resolved spontaneously in 10 patients from group I and in all patients from group II. For the other eight patients in group I, the diarrhoea required MMF discontinuation in three patients and dose reduction in five patients. CONCLUSIONS: In conclusion, in this questionnaire-based evaluation, the incidence of GI disorders was similar in patients receiving either MMF or EC-MPS during the first year post-transplantation.     

Conversion to enteric-coated mycophenolate sodium from various doses of mycophenolate mofetil: results of a prospective international multicenter trial in maintenance renal transplant patients receiving cyclosporine

Conversion from mycophenolate mofetil (MMF, CellCept) to enteric-coated mycophenolate sodium (EC-MPS, myfortic) is safe and effective in renal transplant patients treated with the standard dose of 2 g MMF. In this 6-month, international, multicenter, open-label, single-arm trial, a large cohort of maintenance renal transplant patients receiving different doses of MMF were converted under normal clinical conditions to equimolar doses of EC-MPS. Mean calculated creatinine clearance remained stable from the time of study entry (59.6 +/- 19.7 mL/min) to the end of the study (58.3 +/- 19.8 mL/min). Adverse events were reported by 152 patients (67%), with gastrointestinal complications being observed in 45 patients (20%). Thirty-three patients (15%) experienced adverse events or infections with a suspected relation to EC-MPS, including one case of anemia and two cases of leukopenia. Eleven patients (4.9%) required a reduction in EC-MPS dose and seven patients (3.1%) permanently discontinued EC-MPS owing to adverse events. At month 6 after conversion, five patients (2.2%) experienced biopsy-proven acute rejection. There were no graft losses or deaths. These data support earlier findings that stable maintenance renal transplant patients receiving MMF with cyclosporine with or without corticosteroids can be converted to EC-MPS with no compromise in efficacy and tolerability, and no adverse effect on renal function.     

Quality of life in renal transplant recipients following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium

INTRODUCTION: Tolerance to immunosuppresant treatment has considerable impact on adherence to therapy and on the outcome of renal transplantation. Recent data indicate better gastrointestinal tolerance to enteric-coated mycophenolate sodium (EC-MPS) than to the classic mycophenolate mofetil (MMF) formulation. AIM: This study assessed the effect of conversion therapy from MMF to EC-MPS on gastrointestinal tolerance and quality of life in renal transplant recipients. METHODS: This open observational study analyzed the outcomes of conversion from MMF to EC-MPS among renal transplant patients with gastrointestinal complaints. At baseline (B) and at 8 weeks postconversion patients were assessed by the Gastrointestinal Quality of Life Index (GIQLI) questionnaire as well as by clinical evaluation (acute rejection, infection) and analytical determinations. RESULTS: We analyzed 18 recipients of cadaveric renal transplants of mean age of 54 +/- 9 years including 61% men and one retransplant. Our patients had stable renal function with mean creatinine of 1.9 +/- 0.7 mg/dL. Baseline treatment included cyclosporine-MMF-prednisone (33%) or FK-MMF-prednisone (66%). Bioequivalent conversion was carried out at 50 +/- 29 months posttransplantation. Conversion to EC-MPS resulted in an improvement in overall quality of life (total score: baseline 106.61 vs 8 weeks 116.89; P < .01). Improvements were observed in the following GIQLI subscales: gastrointestinal symptoms (3.12 vs 3.48, P < .001), physical function (2.54 vs 2.76, P = .003), medical treatment (2.17 vs 2.50, P = .031), and emotion (3.08 vs 3.39, P = .001). No changes were observed in the social function subscale. The hemogram and renal function remained stable; there were no episodes of rejection or infection. CONCLUSION: Conversion from MMF to an EC-MPS formulation was associated with improvements in gastrointestinal complaints and quality of life among renal transplant recipients.     

Mycophenolic acid metabolite profile in renal transplant patients receiving enteric-coated mycophenolate sodium or mycophenolate mofetil

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is an effective immunosuppressive treatment in renal transplant recipients but is known to have gastrointestinal side effects. Enteric-coated mycophenolate sodium (EC-MPS; myfortic) is a new formulation for delivering MPA. This open-label, two-period, cross-over study was carried out to characterize the time course of MPA and its metabolites, mycophenolic acid glucuronide (MPAG) and acyl mycophenolic acid glucuronide (AcMPAG) in stable renal transplant patients (n = 40) after 28-day chronic dosing with EC-MPS (720 mg bid) or MMF (1000 mg bid). The relative abundance and exposure of all three compounds was also assessed. EC-MPS demonstrated the typical pharmacokinetic profile of an enteric-coated formulation with a delayed release of MPA compared with MMF (Tmax 2.5 versus 1.0 hours, respectively). Consistent with a similar disposition of MPA, both EC-MPS and MMF treatments resulted in the same ratio of MPAG to MPA exposure, 23:1. Furthermore, comparison of the AUC of MPAG and AcMPAG for both treatments indicated that steady state MPAG exposure was 75 to 90 times that of AcMPAG, confirming MPAG as the predominant metabolite of MPA. AcMPAG has been identified as a possible active metabolite of MPA; the present study indicates that AcMPAG may contribute around 14% of the exposure to active drug after administration of MPA. Both EC-MPS and MMF treatments were well tolerated over the 1-month period of chronic treatment. In summary, consistent with its enteric-coated design, EC-MPS delays delivery of MPA, but results in similar exposure to that provided by MMF.     

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in maintenance renal transplant recipients receiving tacrolimus: clinical, pharmacokinetic, and pharmacodynamic outcomes

BACKGROUND: Mycophenolic acid (MPA) pharmacokinetics using the mycophenolate mofetil (MMF) formulation are known to differ between patients receiving tacrolimus or cyclosporine, but only limited data exist concerning concomitant use of tacrolimus and enteric-coated mycophenolate sodium (EC-MPS). METHODS: In this six-month, multicenter, open-label, single-arm trial, 63 maintenance renal transplant patients receiving tacrolimus were converted from mycophenolate mofetil (MMF) to EC-MPS. RESULTS: MPA concentration-time profiles in 21 patients showed that MPA exposure was similar with MMF or EC-MPS (mean area under the curve 39.9+/-11.6 microg x h/mL versus 43.7+/-17.4 microg x h/mL at day 14 post-conversion). Median time to peak concentration was 0.5 hr with MMF and 1.5 hr with EC-MPS. Inosine monophosphate dehydrogenase (IMPDH) activity was almost identical: area under the enzyme activity time curve (AEC) was 124.2+/-32.0 nmol x h/mg prot/h with MMF and 130.3+/-36.6 nmol x h/mg prot/h with EC-MPS at 14 days post-conversion; average daytime IMPDH activity was 10.3+/-2.7 nmol/h/mg protein and 10.9+/-2.7 nmol/h/mg protein, respectively. Maximal daytime inhibition of IMPDH activity was 67% with MMF and 62% with EC-MPS at day 14. One patient (1.6%) experienced mild biopsy-proven acute rejection. No graft losses or deaths occurred. Renal function remained stable (mean calculated creatinine clearance 70.6+/-26.8 mL/min with MMF and 68.8+/-25.4 mL/min six months post-conversion). Adverse events or infections with a suspected relation to EC-MPS occurred in 12 patients (19%). Four patients discontinued EC-MPS due to adverse events or infections. CONCLUSIONS: MMF and EC-MPS are associated with similar MPA exposure and equivalent pharmacodynamic effect. Conversion of tacrolimus-treated maintenance renal transplant patients from MMF to EC-MPS is safe and well-tolerated and does not compromise therapeutic efficacy.     

Safety assessment of the conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in stable renal transplant recipients

The immunosuppressant mycophenolate mofetil (MMF; CellCept) has greatly improved transplant recipients' clinical outcomes, but its efficacy may be limited by dose adjustments due to adverse events (AEs). An enteric-coated formulation of mycophenolate sodium (EC-MPS; myfortic), designed to improve gastrointestinal tolerability is now available. This Latin-American, prospective, multicenter, open-label, 6-month trial assessed the safety and tolerability of converting renal transplant recipients from MMF to EC-MPS. In total, 237 renal transplant recipients (stable > or = 3 months' posttransplant) receiving MMF (< or =1000 mg b.i.d.) were enrolled. Adults (n = 218) were converted to EC-MPS 720 mg b.i.d. (equimolar to MMF 1000 mg b.i.d.) even if they were initially receiving <1000 mg MMF b.i.d. (ie, 47 adults received a higher than equimolar dose of EC-MPS). Children (n = 19) were converted to EC-MPS 450 or 432 mg/m2 b.i.d. Patients also received cyclosporine microemulsion (Neoral) and corticosteroids. There were three acute rejections and no graft failures. The incidence of AEs was 59.9% (in those receiving a higher than equimolar EC-MPS dose it was 57.4%). In all, 22% of patients had gastrointestinal AEs, 37% had infections, and 4.8% had hematological AEs. Only 24 patients (10%) had an AE-related dose reduction. Seven of these patients had received higher than equimolar doses of EC-MPS. Patients can be safely converted from different doses of MMF to a standard dose of EC-MPS. The requirement for EC-MPS dose reduction to manage AEs was relatively low. Use of EC-MPS is a valid alternative for renal transplant recipients receiving maintenance MMF treatment.     

Reduction of gastrointestinal complications in renal graft recipients after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium

Gastrointestinal (GI) complications such as diarrhea or indigestion frequently occur in renal graft recipients treated with mycophenolate mofetil (MMF), requiring dose reductions to reduce side effects, thereby increasing the risk of rejection episodes and graft loss. In a prospective clinical trial, the immunosuppressive therapy of renal graft recipients was converted from MMF to enteric-coated mycophenolate sodium (EC-MPS) to identify a strategy to reduce GI symptoms without dose reduction. At baseline and 6-8 weeks later patients filled in 4 questionnaires related to GI symptoms and general and health-related quality of life. In 15 German study centers, 196 renal graft recipients (mean age 49.5 ± 13.5 years; male/female, 120/76) were included; 51.0% of patients suffered from GI complications at baseline. The Gastrointestinal Symptom Rating Scale score decreased significantly (P < .001) in patients with GI complications from 2.61 ± 0.86 at baseline to 2.14 ± 0.86 at visit 2. Health-related and general quality of life improved significantly. Fifty percent of patients with GI symptoms and 34% of the total per protocol population reported an improvement of their physical condition after converting the medication. In conclusion, conversion from MMF to EC-MPS reduces GI complications in renal graft recipients, reduces the patients' physical discomfort, and maintains their quality of life.(ClinicalTrials.gov number NCT00149968.)     

Better mycophenolic acid 12-hour trough level after enteric-coated mycophenolate sodium in patients with gastrointestinal intolerance to mycophenolate mofetil

INTRODUCTION: Enteric-coated mycophenolate sodium (EC-MPS) is the enteric-coated salt form of mycophenolic acid (MPA), the active component of the prodrug mycophenolate mofetil. EC-MPS was developed to reduce the upper-gastrointestinal (GI) effects of mycophenolate mofetil. There are no studies available comparing trough plasma levels in patients with GI intolerance to MMF when they are converted to EC-MPS. AIM: To compare the GI tolerance and the MPA levels in patients previously treated with MMF in whom this drug was replaced by EC-MPS. MATERIALS AND METHODS: A prospective study was conducted in 133 renal transplant patients after conversion from MMF to EC-MPS (median time posttransplant 42 months, range 1 to 240 months). The causes for EC-MPS switching were GI intolerance to MMF (51.9%; group A), low trough plasma levels with MMF (29.3%; group B), and others (18.8%; group C). These patients were converted to equipotent doses of EC-MPS. RESULTS: The trough plasma MPA levels increased from 1.5 +/- 1.1 microg/mL at baseline to 2.5 +/- 2.0 microg/mL at 1 month postconversion despite the equipotent EC-MPS doses not being increased. These higher plasma levels were maintained throughout the study. In group A, this increase was from 1.8 +/- 1.0 to 2.7 +/- 2.1 microg/mL (P = .01) and in group B from 0.8 +/- 0.4 to 2.4 +/- 1.4 microg/mL (P < .001). The doses and levels of calcineurin inhibitor decreased from baseline. Creatinine clearance improved from 56.5 +/- 24.7 mg/dL at baseline to 61.9 +/- 28.6 at 6 months postconversion (P = .02). There was a statistically significant increase in hemoglobin levels. In group A, the GI tolerance improved in 78% of the patients. CONCLUSIONS: At equipotent doses, patients converted to EC-MPS have higher and more adequate levels of MPA. At 6 months postconversion, we observed an improvement of the renal function, probably due to a reduction of calcineurin inhibitor drugs. However, the possibility that a better immunosuppressive efficacy as demonstrated by more suitable trough plasma levels may have been a contributing factor cannot be discarded.     

Patient-reported gastrointestinal symptom burden and health-related quality of life following conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium

BACKGROUND: The benefit of converting renal transplant recipients with gastrointestinal (GI) complaints from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) has not been evaluated using patient-reported outcomes. METHODS: A multicenter, open-label, prospective study was undertaken in MMF-treated renal transplant patients. Patients experiencing GI complaints were converted to equimolar EC-MPS (Cohort A). Patients without GI complaints remained on MMF (Cohort B). At baseline and Visit 2 (4-6 weeks postbaseline), patients completed the Gastrointestinal Symptom Rating Scale (GSRS), Gastrointestinal Quality of Life Index (GIQLI) and Psychological General Well-being Index (PGWBI). At Visit 2, patients and physicians completed the Overall Treatment Effect (OTE) scale for GI symptoms. Additionally, patients completed the OTE for health-related quality of life (HRQoL). Minimal important difference (MID) was calculated for GSRS and GIQLI based on patients' and physicians' OTE evaluation. RESULTS: Of 328 patients enrolled (i.e. the intent-to-treat and safety populations), 278 formed the per-protocol population (Cohort A, n=177; Cohort B, n=101). At baseline, Cohort A had significantly worse scores on all GSRS, GIQLI and PGWBI subscales compared to Cohort B (all P<0.0001). All GSRS, GIQLI and PGWBI subscale scores improved significantly in Cohort A between baseline and Visit 2 (all P<0.0001). Mean improvements in all GSRS subscales and most GIQLI subscores exceeded the calculated MID. GSRS, GIQLI and PGWBI subscales remained stable in Cohort B. CONCLUSION: This first exploratory study indicates that converting patients with mild, moderate or severe GI complaints from MMF to EC-MPS significantly reduces GI-related symptom burden and improves patient functioning and well-being.     

吗替麦考酚酯与麦考酚钠肠溶片对肾移植受体血药浓度的影响

目的  探讨吗替麦考酚酯（MMF）与麦考酚钠肠溶片（EC-MPS）在同等生物效应剂量下对肾移植受体麦考酚酸（MPA）血药浓度和不良反应的影响。方法  回顾性分析106例活体供肾移植受体的临床资料。按肾移植术后服用不同药物分为两组,MMF组（M1组,62例）和EC-MPS组（M2组,44例）。两组受体的免疫抑制方案分别为M1组用他克莫司（FK506）+MMF+泼尼松,M2组用FK506+EC-MPS+泼尼松。分析两组受体服药后1、2、3周和1、2、3个月MPA血药浓度的变化情况、不良反应发生情况及服用药物所花费用。结果  采取同等生物效应给药,服药后第1、2、3周,第1、2、3个月时M1组MPA血药谷浓度比M2组低,各个时间点两组间比较,差异均有统计学意义（均为P < 0.05）。与M1组比较,M2组术后不良反应的发生率较低且症状较轻。采用同等生物学效应给药,M1组服用MMF所花费用1 710元/月,M2组服用EC-MPS所花费用2 736元/月,但M1组因治疗药物不良反应所产生费用远高于M2组。结论  同等的生物效应剂量下服用EC-MPS的患者相对服用MMF的患者能维持更高的MPA血药浓度并且不良反应更少。     

Safety and efficacy after conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium: results of a 1-year extension study

Enteric-coated mycophenolate sodium (EC-MPS) is an enteric-coated formulation of mycophenolic acid. A 12-month, multicenter, double-blind, randomized clinical study demonstrated that converting maintenance renal transplant patients from mycophenolate mofetil (MMF) to EC-MPS is safe and does not affect efficacy. In an open-label study extension, 130 patients initially randomized to MMF were converted to EC-MPS (newly exposed); 130 initially randomized to EC-MPS continued on EC-MPS (EC-MPS long-term). A composite endpoint of biopsy-proven acute rejection (BPAR), graft loss, or death occurred in 3 (2.3%) newly exposed and 2 (1.5%) EC-MPS long-term patients during the extension phase. One patient died and one lost his graft. BPAR occurred in 3 (2.3%) newly exposed patients and 1 (0.8%) EC-MPS long-term patient. During the first 12 months of the extension phase, incidence and type of adverse events was similar in both groups and comparable to that seen in the core study. Nine cases of malignancy were reported, mainly nonmelanoma skin cancers. EC-MPS dose adjustments for adverse events were required in <12% of patients. At the end of the 12-month extension, 58 (44.6%) and 64 (49.2%) newly exposed and EC-MPS long-term patients, respectively, had reported at least one gastrointestinal adverse event. Mean serum creatinine remained stable at the 12-month visit of the extension study (137 micromol/L in the newly exposed and 142 micromol/L in the EC-MPS long-term groups). The results of this study demonstrate the long-term safety of EC-MPS and reconfirm the safety of converting MMF maintenance renal transplant patients to EC-MPS.     

Pharmacokinetics of enteric-coated mycophenolate sodium in stable liver transplant recipients

INTRODUCTION: Mycophenolate mofetil (MMF) is one of the major immunosuppressive agents used in liver transplantation recipients. In an attempt to mitigate one of the most common side effects of MMF (gastrointestinal symptoms), enteric-coated mycophenolate sodium (EC-MPS) was developed. In this study, we report the pharmacokinetic profile of EC-MPS in stable liver transplantation recipients administered a single 720 mg dose. METHODS: Liver transplantation recipients more than one yr after transplantation were administered a single dose of 720 mg EC-MPS after which blood levels of MPA were measured at frequent intervals using a specific and validated LC-MS/MS assay. RESULTS: The characteristics of the 21 patients studied were: mean age was 55.9 yr, 13 were female, eight had hepatitis C, and 14 were on tacrolimus. The mean apparent half-life of MPA was 5.3 +/- 4.3 h, (1.0-15.7). Mean t(max) was 2.4 +/- 1.1 h (1.0-5.0). The mean area-under-curve was 45.3 +/- 23.1 microg-h/mL (17.3-90.0). Trough level concentrations (C(12 h)) showed large inter-individual variability (0-9.2 microg/mL). There was no difference in any of the pharmacokinetic parameters relative to: gender, HCV, administration of tacrolimus vs. cyclosporine or type of biliary anastomosis. CONCLUSIONS: There is a wide variation in pharmacokinetic parameters in stable, long-term liver transplantation recipients receiving a single dose of EC-MPS. These data suggest that therapeutic drug monitoring with EC-MPS may have limited utility in liver transplantation recipients.