RESUMO
Lichen planopilaris (LPP) is a chronic inflammatory disorder of hair without a proven effective and safe treatment. To objectively assess the clinical efficacy of mycophenolate mofetil (MMF) in patients suffering from LPP, a retrospective cohort study was conducted on 52 patients who treated with MMF (2 g/day) at least for 6 months. LPP activity index (LPPAI) before and after treatment was calculated and compared. Most of the patients were female and belonged to the age group of 50-60 years. All of the disease activity indices were significantly improved after 6 months of therapy (p < 0.001). The majority of patients had LPPAI 4-6 and 0-2, before and after treatment, respectively. After 6 months of treatment, half of patients showed a disease activity decrease (LPPAI reduced >25% compared to the baseline value). Systemic MMF is an effective and relatively safe treatment modality for patients with LPP and could lead to significant reduction in disease activity regarding both subjective and objective indices.
Assuntos
Líquen Plano , Feminino , Humanos , Imunossupressores/efeitos adversos , Líquen Plano/induzido quimicamente , Líquen Plano/diagnóstico , Líquen Plano/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The aim of the present study was to investigate the clinical outcome of mycophenolate mofetil in pediatric refractory gastrointestinal (GI) Henoch-Schönlein purpura (HSP). Most of the HSP patients with GI symptoms may benefit from early introduction of glucocorticoid; however, a number of patients still do not achieve remission following the administration of steroids. Therefore, the present study was to investigate the clinical features and the clinical outcome of mycophenolate mofetil in refractory GI HSP. A total of 110 HSP patients with a median onset age of 6.3 years were included. Sixty-one (55.5%) exhibited GI involvement, and 18 (18/61, 29.5%) presented with refractory GI involvement, with a median onset age of 6.3 years. Intractable abdominal pain, GI hemorrhage, intussusception, and chronic ulcers were common presentations of GI involvement. Of those refractory ones, Arthralgia was observed in 9 cases and renal involvement was observed in 13 cases. Glucocorticoids were administered in all 18 patients, but remission was not achieved. However, complete remission of abdominal pain was achieved in all patients within a median time of 3 days (1-14 days) after mycophenolate mofetil therapy. The infection rate of Epstein-Barr virus and cytomegalovirus in the refractory group was significantly higher compared with that in non-refractory group.Conclusion: GI symptoms in HSP patients with refractory GI involvement were more severe compared with non-refractory cases. Epstein-Barr virus and cytomegalovirus infection may be risk factors for refractory GI HSP. The efficacy of mycophenolate mofetil treatment was evident in these patients. What is Known: ⢠Abdominal pain, gastrointestinal hemorrhage, intussusceptions, and intestinal perforation were the main presentations of gastrointestinal involvement in Henoch-Schönlein purpura. What is New: ⢠Epstein-Barr virus and Cytomegalovirus infection may be the high risk factor of refractory GI. Refractory gastrointestinal Henoch-Schönlein purpura was associated with renal involvement. ⢠Mycophenolate mofetil treatment was effective for refractory gastrointestinal Henoch-Schönlein purpura.
Assuntos
Infecções por Vírus Epstein-Barr , Gastroenteropatias , Vasculite por IgA , Criança , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/etiologia , Herpesvirus Humano 4 , Humanos , Vasculite por IgA/complicações , Vasculite por IgA/tratamento farmacológico , Ácido Micofenólico/efeitos adversosRESUMO
Using square wave voltammetry, a carbon paste electrode modified by molecularly imprinted polymer (MIP) as a recognition element of mycophenolate mofetil (MMF) and multi-walled carbon nanotubes was used for MMF monitoring To investigate the electrode during modification, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) were utilized. After optimization of the effective parameters, the anodic peak current of MMF was utilized for dynamic range study which was linear in 9.9â¯nM-87⯵M range. The detection limit of the sensor was 7.0â¯nM. The capture ability of MIP to target was compared with that of non-imprinted polymer (NIP). The practical application of the sensor in biological fluid samples analysis demonstrates its selectivity, sensitivity, and stability.
Assuntos
Carbono/química , Impressão Molecular , Ácido Micofenólico/análise , Nanotubos de Carbono/química , Polímeros/química , Técnicas Eletroquímicas , Eletrodos , Voluntários Saudáveis , Humanos , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de SuperfícieRESUMO
A simple and sensitive method based on adsorptive anodic stripping differential pulse voltammetry (AASDPV) for the determination of cellcept, using a magnetic Fe3O4 nanoparticles and functionalized (carboxylated) multi-walled carbon nanotubes modified glassy carbon electrode (f-MWCNs/Fe3O4/GCE) was developed. In phosphate buffer solution (pH = 5), the voltammogram of cellcept exhibited tow anodic peaks and the well-defined peak at about 0.611 V vs SCE was used for its monitoring. The modified electrode was characterized by different methods such as electrochemical impedance spectroscopy (EIS), scanning electron microscopy (SEM) and cyclic voltammetry (CV). The experimental parameters, such as pH, deposition potential and time, as well as scan rate were optimized. Under the optimized conditions, Ip (µA) was proportional to the cellcept concentration in the range of 0.05-200 µM (R2 = 0.9989) with a detection limit of 9.0 nM and limit of quantification of 30.2 nM. The recovery was >98%. The practical analytical utilities of the modified electrode were demonstrated by the determination of cellcept in human urine and blood serum samples. Modified electrode showed an adequate sensitivity and stability for evaluated samples.
Assuntos
Técnicas Eletroquímicas , Óxido Ferroso-Férrico/química , Nanopartículas de Magnetita/química , Ácido Micofenólico/análise , Nanotubos de Carbono/química , Adsorção , Carbono/química , Espectroscopia Dielétrica , Eletrodos , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Microscopia Eletrônica de Varredura , Ácido Micofenólico/sangue , Ácido Micofenólico/urina , Oxirredução , Reprodutibilidade dos Testes , SonicaçãoRESUMO
MORE was a four-yr, prospective, observational study at 40 transplant centers in the US. Data were analyzed to evaluate changes in mycophenolic acid (MPA) dosing over time in 904 de novo kidney transplant recipients receiving enteric-coated mycophenolate sodium (EC-MPS, n = 616) or mycophenolate mofetil (MMF, n = 288) with tacrolimus. Induction therapy and steroid treatment were similar in the two subpopulations. The proportion of patients receiving the maximal recommended MPA dose was 80.5%, 43.9%, 39.2%, 34.6%, and 30.1% at baseline and years 1, 2, 3, and 4, respectively. More patients received the maximal recommended MPA dose with EC-MPS vs. MMF at month 1 (79.2% vs. 71.7%, p = 0.016), month 3 (68.5% vs. 56.9%, p = 0.001), and month 6 (52.9% vs. 44.0%, p = 0.028). Multivariate analysis showed the risk of biopsy-proven acute rejection, graft loss or death to be similar for EC-MPS vs. MMF. Estimated glomerular filtration rate (GFR) was similar with EC-MPS vs. MMF at all time points. There were no significant differences in any category of adverse event between the EC-MPS and MMF cohorts during follow-up, including gastrointestinal events. In conclusion, MPA dose was maintained more effectively in the first six months after kidney transplantation using EC-MPS vs. MMF, without an increase in adverse events.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/administração & dosagem , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Comprimidos com Revestimento Entérico/administração & dosagem , Tacrolimo/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Falência Renal Crônica/cirurgia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Prognóstico , Estudos Prospectivos , Fatores de RiscoRESUMO
Mycophenolic acid Observational REnal transplant (MORE) was a prospective, observational study of de novo kidney transplant patients receiving mycophenolic acid (MPA). Four-yr data on 904 patients receiving tacrolimus and enteric-coated mycophenolate sodium (EC-MPS) or mycophenolate mofetil (MMF) were analyzed to evaluate immunosuppression and graft outcomes in African American (AA, n = 218) vs. non-AA (n = 686) patients. Mean tacrolimus dose was higher in AA vs. non-AA patients but mean tacrolimus trough concentration was similar. Use of the recommended MPA dose in AA patients decreased from 78.9% at baseline to 33.1% at year 3. More AA patients received the recommended MPA dose with EC-MPS than MMF at month 6 (56.2% vs. 35.7%, p = 0.016) and month 36 (46.6% vs. 16.7%, p = 0.029), with no safety penalty. Significantly, more AA patients received corticosteroids than non-AA patients. Biopsy-proven acute rejection was higher in AA vs. non-AA patients (18.9% vs. 10.7%, p = 0.003), as was graft loss (10.9% vs. 4.4%, p = 0.003); differences were confirmed by Cox regression analysis. Patient survival was similar. Estimated GFR was comparable in AA vs. non-AA patients. Kidney allograft survival remains lower for AA vs. non-AA recipients even under the current standard of care.
Assuntos
Negro ou Afro-Americano/estatística & dados numéricos , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Ácido Micofenólico/análogos & derivados , Adulto , Feminino , Seguimentos , Taxa de Filtração Glomerular , Humanos , Terapia de Imunossupressão , Falência Renal Crônica/etnologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Prognóstico , Estudos Prospectivos , Fatores de TempoRESUMO
The use of generic immunosuppressive agents is controversial, especially for the treatment of pediatric patients, as information on the bioavailability of generic immunosuppressants in children is particularly scarce. The aim of the study was to compare the bioavailabilities of two products containing mycophenolate mofetil, the innovator and a generic, in children. Pediatric patients with end-stage renal disease on the waiting list for renal transplantation received a single oral dose of mycophenolate mofetil as either the innovator product (CellCept(®) , Roche) or the generic (Tevacept(®) , Teva Pharmaceuticals). A nine point pharmacokinetic profile was obtained. Mycophenolic acid concentration was quantitated in plasma by HPLC, plasma concentration-against-time curves were constructed, and bioavailability parameters were determined. Pharmaceutical quality analysis of both formulations, including drug content and dissolution profile, was also performed. There were no statistically significant differences between formulations in bioavailability parameters. Interindividual variability was very important, but individual values of AUC, an indicator of the extent of drug absorption, were within the same range for both formulations. The two formulations exhibited similar drug content and dissolution profiles, as well as comparable mycophenolic acid plasma levels in an end-stage renal failure population.
Assuntos
Medicamentos Genéricos/farmacocinética , Imunossupressores/farmacocinética , Ácido Micofenólico/análogos & derivados , Administração Oral , Adolescente , Área Sob a Curva , Disponibilidade Biológica , Criança , Cromatografia Líquida de Alta Pressão , Medicamentos Genéricos/química , Feminino , Humanos , Imunossupressores/química , Transplante de Rim , Masculino , Ácido Micofenólico/química , Ácido Micofenólico/farmacocinética , Projetos PilotoAssuntos
Colite/induzido quimicamente , Colo/efeitos dos fármacos , Imunossupressores/efeitos adversos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Ácido Micofenólico/efeitos adversos , Pancreatite/induzido quimicamente , Adulto , Biópsia , Colite/diagnóstico , Colo/patologia , Colonoscopia , Diarreia/induzido quimicamente , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Pancreatite/diagnósticoRESUMO
Although corticosteroids are currently the first-choice drug for thyroid eye disease (TED), in 20-30% of cases, patients show poor or non-existent responses, and when the drug is withdrawn, 10-20% of patients relapse. Thus, in this study, we aimed to investigate the efficacy of the combined use of mycophenolate mofetil (CellCept®) and low dose oral prednisolone in patients with moderate to severe Graves' orbitopathy (GO). For the first time, we investigated the relationship between TED-related parameters and proptosis reduction. In a prospective, non-randomized, interventional case series, 242 patients with moderate-to-severe GO were, assigned to receive oral prednisolone (5 mg/ d) and mycophenolate mofetil (CellCept®) (one 500 mg tablet twice per day according to the therapeutic response). The patients were monitored regularly during the 3rd, 6th, 12th, and 18th month of treatment. The main outcome measures were the clinical activity score (CAS), intraocular pressure (IOP), diplopia, proptosis and visual acuity. We also assessed the relationship between the main outcomes with proptosis changes and time to improvement (months). Adverse effects were recorded during each visit. The clinical response rate increased from 67.7% on the third month to 89.2% on the sixth month, and 94.2% on the 12th month. This therapeutic response continued until the 18th month of follow-up. The CAS responses [disease inactivation (CAS <3)] improved during our study: 70.6% on the third month, 90.0% on the sixth month, and 92.5% at 12th month. These conditions continued until the 18th month of follow-up. Proptosis improvement was 52% on the third month, 71% on the sixth month, 83% on the 12th month, and 87.1% on the 18th month. Changes in IOP and visual acuity were not significant (P = 0.568 and 0.668, respectively). The patient showed significant improvement in the Gorman score. A Shorter duration of treatment was seen in patients with earlier onset of intervention, younger age, and lack of all extraocular muscle (EOM) enlargement on computed tomography (CT) scan (p < 0.05). In addition, a better response (more reduction) in proptosis was related to: younger age at disease, earlier treatment intervention (less interval from the time the diagnosis of moderate-to-severe GO was made until medication initiation), shorter treatment time (less time to improvement), less IOP, lack of EOM enlargement on CT scan, and lack of diplopia (P < 0.05). Adverse events occurred in six patients. Findings show that mycophenolate mofetil (CellCept®) plus low-dose prednisolone can be introduced as a new optimal dosing regimen in GO due to its better effect on chronic complications such as proptosis and diplopia.
RESUMO
PURPOSE: There is no universal consensus on second-line agents for the treatment of moderate/severe to sight-threatening thyroid eye disease (TED) to maintain remission after first-line intravenous methylprednisolone (IVMP). This study investigates the efficacy and safety of mycophenolate mofetil (MMF) in TED patients in a real-world setting and over a longer period than previous randomized controlled trials. METHODS: A retrospective cohort study of TED patients with active moderate/severe to sight-threatening TED seen over a 4-year period. Data collected were visual acuity (VA), Clinical Activity Score (CAS), Gorman Diplopia scores, MMF dosing and side effects at 24, 52 and 78 weeks. Clinical efficacy was defined as an absence of relapse: no decline in best corrected LogMAR VA, no need for further steroids, no increase in CAS of ≥2. RESULTS: Out of 23 patients, 20 patients were included in this study. 10% (2/20) stopped MMF before 24 weeks. Median duration of MMF treatment was 76 weeks (1-140 weeks). 55% (11/20) had dysthyroid optic neuropathy (DON). In those with active moderate-severe TED without DON, clinical efficacy was seen in 100% (8/8) at 24 weeks, 87.5% (7/8) at 52 weeks, and 83.3% (5/6) at 78 weeks, with CAS decreasing from a baseline of 2.78±1.99 to 0.50±0.58 at 24 weeks, 0.50±0.82 at 52 weeks and 1.00±1.30 at 78 weeks. In DON, improvements were seen in 90% (9/10) at 24 weeks, 100% (7/7) at 52 weeks and 100% (4/4) at 78 weeks, with significantly reduced CAS scores from 2.55±1.54 to 0.83±1.27, 1.00±1.17 and 0.63±0.95 at 24, 52 and 78 weeks, respectively. Gorman score, VA and soft tissue inflammation parameters also improved throughout. There were two significant side effects over the treatment period. CONCLUSION: MMF appears to be an effective and safe second-line immunosuppressive agent. Further studies aimed at elucidating optimal dosing regimens and ideal treatment duration will prove helpful.
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Glioblastoma multiforme (GBM) is a highly malignant primary brain tumor. The current standard of care for GBM is the Stupp protocol which includes surgical resection, followed by radiotherapy concomitant with the DNA alkylator temozolomide; however, survival under this treatment regimen is an abysmal 12-18 months. New and emerging treatments include the application of a physical device, non-invasive 'tumor treating fields' (TTFs), including its concomitant use with standard of care; and varied vaccines and immunotherapeutics being trialed. Some of these approaches have extended life by a few months over standard of care, but in some cases are only available for a minority of GBM patients. Extensive activity is also underway to repurpose and reposition therapeutics for GBM, either alone or in combination with the standard of care. In this review, we present select molecules that target different pathways and are at various stages of clinical translation as case studies to illustrate the rationale for their repurposing-repositioning and potential clinical use.
RESUMO
Purpose To investigate the effect of CellCept nanoliposomes on Adriamycin-induced nephrotic syndrome in rats. Methods To model nephrotic syndrome, rats were injected with 6.5 mg/kg of Adriamycin in the tail vein. The rats were randomly divided into three groups, including a control group, a free mycophenolate mofetil (MMF)-treated group, and a liposome-encapsulated MMF-treated group. Five weeks after the Adriamycin treatment, the free MMF-treated group received CellCept while the liposome-encapsulated MMF-treated group received the CellCept nanoliposomes for 2 weeks. The general condition of the animals was observed, which included urine volume over 24 h, urine protein levels, and serum biochemical indexes. Renal morphology was also observed. Results The level of urine protein over 24 h was increased in the control group, while plasma albumin (ALB) was decreased. The total cholesterol (TC) and triacylglycerol (TG) levels increased significantly (P < 0.05, P < 0.01). The pathological examination of the kidneys showed some abnormalities. In contrast, these parameters were improved significantly in the free mycophenolate mofetil (MMF)-treated and liposome-contained mycophenolate mofetil (MMF)-treated groups. Conclusion The CellCept nanoliposomes have a good therapeutic effect on Adriamycin-induced nephrotic syndrome in rats.
Assuntos
Ácido Micofenólico , Nanopartículas/química , Síndrome Nefrótica/tratamento farmacológico , Animais , Modelos Animais de Doenças , Doxorrubicina/efeitos adversos , Doxorrubicina/farmacologia , Lipossomos , Ácido Micofenólico/química , Ácido Micofenólico/farmacologia , Síndrome Nefrótica/metabolismo , Síndrome Nefrótica/patologia , RatosAssuntos
Implantes de Medicamento/administração & dosagem , Fluocinolona Acetonida/análogos & derivados , Uveíte/tratamento farmacológico , Ensaios Clínicos como Assunto/métodos , Implantes de Medicamento/química , Implantes de Medicamento/farmacocinética , Fluocinolona Acetonida/administração & dosagem , Fluocinolona Acetonida/química , Fluocinolona Acetonida/farmacocinética , Humanos , Injeções Intravítreas , Polímeros/administração & dosagem , Polímeros/farmacocinética , Uveíte/metabolismoAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoAssuntos
Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Nefrite Lúpica/tratamento farmacológico , Administração Oral , Animais , Inibidores de Calcineurina/farmacocinética , Ensaios Clínicos como Assunto/métodos , Ciclosporina/farmacocinética , Humanos , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/metabolismo , Nefrite Lúpica/epidemiologia , Nefrite Lúpica/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismoAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Corticosteroides/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Método Duplo-Cego , Aprovação de Drogas , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença , Estados Unidos , United States Food and Drug AdministrationRESUMO
BACKGROUND: Mycophenolate mofetil (MMF) is an oral DNA base synthesis inhibitor with immunomodulatory effects on B cells, T cells, and macrophages. OBJECTIVE: To conduct a safety and tolerability pilot study of interferon beta-1a (IFN-b1a) in combination with either placebo or oral MMF in multiple sclerosis (MS). METHODS: Twenty-four treatment-naïve R-RMS patients participated in a one-year prospective, placebo-controlled, blinded, safety pilot clinical trial. Every patient injected weekly intramuscular interferon beta-1a. The cohort was then randomized (1 : 1) to either active oral MMF or identical-appearing placebo tablets. Clinical evaluations were assessed every 3 months, along with brain MRI scans performed at baseline and repeated every 60 days for one year. Comprehensive laboratory assessments were monitored for safety, along with adverse events. RESULTS: In this small pilot investigation, no differences were identified between the two treatment groups with respect to patient-reported adverse events, MRI metrics, or laboratory abnormalities. Notwithstanding these observations, and the limited number of patients treated, trends appeared to favor the combination therapy regimen. CONCLUSIONS: The combination treatment regimen of interferon beta-1a and MMF appeared to be well tolerated in this pilot study. Despite the small sample size, therapeutic trends were observed in favor of combination therapy. An adequately powered controlled trial of MMF in MS appears warranted.
RESUMO
BACKGROUND: Mycophenolate mofetil (MMF, CellCept®) has been utilized as an antirejection agent in transplant recipients and in patients with myriad autoimmune disorders including multiple sclerosis (MS). OBJECTIVE: To investigate radiographic and clinical safety involving monotherapy use of daily oral MMF (1 g b.i.d.) versus weekly intramuscular interferon beta 1a (Avonex® at 30 mcg) in relapsing-remitting MS (RRMS). METHODS: We organized a randomized, serial, 6-monthly, MRI-blinded, parallel-group multicenter pilot study to determine the safety of MMF versus interferon beta monotherapy in 35 untreated patients with RRMS, all of whom exhibited evidence of gadolinium (Gd) enhancement on a screening MRI of the brain. The primary outcome was the reduction in the cumulative mean number of combined active lesions (CAL), new Gd-enhancing lesions, and new T2 lesions on MRI analyses. RESULTS: Both interferon beta and MMF appeared safe and well tolerated in the majority of patients. There was no difference between MMF therapy and the standard regimen of interferon beta therapy on the primary safety MRI endpoints of the study. However, the MMF group showed a trend toward a lower accumulation of combined active lesions, CAL, Gd and T2 lesions when compared with interferon beta treated patients. CONCLUSIONS: The results from this pilot study suggest that the application of MMF monotherapy in MS deserves further exploration.
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Mycophenolate mofetil (MMF) has been used to treat myasthenia gravis (MG) for over 10 years. MMF's use in the MG population stems from its theoretical mechanism of action and the medical literature that supports its benefit in MG patients. Recently, two large, double-blinded, placebo-controlled, randomized clinical trials were initiated to study the effectiveness of MMF for MG. One of these studies found no benefit in taking MMF with 20 mg of prednisone as compared to taking prednisone alone, while the other study demonstrated no advantage in taking MMF against placebo during a 36-week prednisone taper. This article critically reviews the medical literature on MMF's use in MG and suggests further research avenues on this topic.