To investigate the effects of mycophenolate mofetil (MMF) on the process of renal interstitial fibrosis, unilateral ureteral obstruction (UUO) model was established in rats. Twenty Sprague-Dawley rats underwent UUO and received vehicle (n = 10) or MMF (20 mg.kg-1.d-1, by daily gastric gavage, n = 10) during a period of 5 days following surgery, and the additional 10 rats were served as sham-operated group. The rats were killed 5 days after surgery. Immunohistochemistry was performed on renal tissue for proliferating cell nuclear antigen (PCNA), alpha-smooth muscle actin (alpha-SMA) and type I and III collagen (col I, col III). Histological studies were also done by MASSON staining. Five days after surgery, proliferating cells in tubules, interstitium as well as interstitial myofibroblast (MyoF) infiltration and interstitial col I, col III deposition were all significantly reduced by MMF treatment. MMF also alleviated the histological changes of UUO rats. These results suggested that the reduction of interstitial MyoF infiltration may be an important event by which MMF prevents renal injury caused by UUO and MMF could be used to limit the progression of renal fibrosis.
Fibrosis ; Kidney/*pathology ; Kidney Diseases/etiology ; Kidney Diseases/pathology ; Kidney Diseases/*prevention & control ; Mycophenolic Acid/*analogs & derivatives ; Mycophenolic Acid/*pharmacology ; Random Allocation ; Rats, Sprague-Dawley ; Ureteral Obstruction/*complications

AIMTo investigate the pharmacokinetics of mycophenolic acid (MPA), an active metabolite of mycophenolate mofetil (MMF) in Chinese adult liver transplant patients.

METHODSThirty-eight liver transplant patients (male 30, female 8) receiving MMF 1.0 g, twice daily in accordance with the recommended regimen were included in this study. Plasma MPA concentrations were measured by high performance liquid chromatography at 0.5, 1, 1.5, 2, 4, 6, 8, 10 and 12 h after the administration of a single dose. Pharmacokinetic parameters were calculated with 3P97 software.

RESULTSThe plasma MPA concentration-time curve was characterized with an early sharp peak reached at 0.5 - 6.0 h after oral administration. And in some patients there was a small second peak due to enterohepatic circulation of mycophenolic acid glucuronide (MPAG), which underwent deglucuronidation and re-absorption as MPA at 4 to 12 h postdose. The mean peak plasma concentration (C(max)) and area under concentration-time curve (AUC(0-12 h)) were (12 +/- 7) microg x mL(-1) and (44 +/- 16) microg x h x mL(-1), respectively. However, a large variability of pharmacokinetic parameters existed in these patients.

CONCLUSIONIn view of the inter-individual variability of MMF pharmacokinetics, plasma MPA concentration should be monitored routinely after MMF administration for individual patient.

Adult ; Aged ; Area Under Curve ; Female ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Liver Transplantation ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; pharmacokinetics

Child, Preschool ; Female ; Humans ; Infant ; Male ; Mycophenolic Acid ; adverse effects ; analogs & derivatives ; therapeutic use ; Nephrotic Syndrome ; drug therapy ; Treatment Outcome

OBJECTIVETo evaluate the clinical efficacy of mycophenolate mofetil (MMF) in the treatment of systemic-onset juvenile idiopathic arthritis (SoJIA).

METHODSThirty-five patients with a confirmed diagnosis of SoJIA who had received initial treatment were randomly divided into control (n=15), MMF1 (n=7) and MMF2 groups (n=13). The control group received conventional treatment, the MMF1 group received MMF after 2 weeks of conventional treatment that had not led to remission, and the MMF2 group received combination therapy with non-steroidal anti-inflammatory drugs, prednisone and MMF. Symptoms, signs, laboratory indices, and adverse events were observed after 2, 4, and 12 weeks of treatment, and follow-up was performed for 3-6 months.

RESULTSBefore treatment, the MMF2 group had a significantly longer disease course than the control group (P<0.05). After 2 weeks of treatment, the MMF1 and MMF2 groups had a significantly lower prednisone dose and erythrocyte sedimentation rate (ESR) than the control group (P<0.05). The MMF1 group had significantly higher body temperature than the other two groups (P<0.05). After 4 weeks of treatment, the MMF1 group had a significantly lower prednisone dose and ESR than the control group (P<0.05). The MMF2 group had a significantly lower prednisone dose, body temperature (recovery to normal), white blood cell count, ESR and serum ferritin concentration than the control group (P<0.05). Body temperature was significantly lower in the MMF2 group than in the MMF1 group (P<0.05). No adverse events were observed in either the MMF1 or MMF2 groups during treatment.

CONCLUSIONSCombination therapy with MMF can lead to better control of the patient's condition, more rapid relief of clinical symptoms and reduced glucocorticoid dose. The therapy with MMF is safe in children.

Arthritis, Juvenile ; blood ; drug therapy ; Blood Sedimentation ; Child, Preschool ; Female ; Humans ; Immunosuppressive Agents ; therapeutic use ; Male ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Prednisone ; therapeutic use

Adult ; Female ; Humans ; Lupus Erythematosus, Systemic ; drug therapy ; Methylprednisolone ; therapeutic use ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Neuromyelitis Optica ; drug therapy ; Prednisone ; therapeutic use ; Young Adult

AIMTo develop a pharmacokinetic model for the enterohepatic circulation of mycophenolic acid (MPA).

METHODSTwenty healthy volunteers were orally given a single dose of 500 mg mycophenolate mofetil. Plasma samples were collected during 48 hours and MPA concentration was measured by HPLC method. Pharmacokinetic (PK) model was established based on physiological and biopharmaceutical consideration and PK parameters were obtained using nonlinear mixed effect model.

RESULTSThe proposed model included an intestinal compartment and gall bladder compartment in addition to the central compartment. The predicted time-concentration curve and AUC0-t, Cmax, Tmax estimated by the established model were in agreement with the observations.

CONCLUSIONThe established model was well defined for the MPA disposition and could afford a useful approach for the further clinical investigation.

Adult ; Area Under Curve ; Enterohepatic Circulation ; physiology ; Glucuronides ; pharmacokinetics ; Humans ; Immunosuppressive Agents ; pharmacokinetics ; Male ; Models, Biological ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics

To assess the influence of cyclosporin A (CsA) and tacrolimus (FK506) on mycophenolic acid (MPA) and correlation analysis of the pharmacokinetic parameters and patient characteristics, clinical outcome in Chinese kidney transplant recipients, the pharmacokinetics of 1000 mg mycophenolate mofetil (MMF) twice daily was measured by high-performance liquid chromatography (HPLC). PKS (Pharmaceutical Kinetics Software) 1.0.2 software package was used for the calculation of pharmacokinetic parameters. The mean C(max), t(max), and AUC((0-12))were (21.88+/-10.52) microg/ml, (1.20+/-0.95) h, and (52.546+/-13.215) microg.h/ml, respectively. The level of AUC((0-12)) in the FK506 group was significantly higher than that in the CsA group. MPA appeared not to be affected by renal function. MPA AUC((0-12)) showed statistically significant difference according to the patient's gender.
Adult ; Cyclosporine ; administration & dosage ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; pharmacokinetics ; Kidney Transplantation ; physiology ; Male ; Middle Aged ; Mycophenolic Acid ; administration & dosage ; analogs & derivatives ; pharmacokinetics ; Tacrolimus ; administration & dosage

OBJECTIVETo analyze the clinical features of mid- and long-term acute cardiac allograft rejection to improve the long-term clinical outcomes of the patients.

METHODSFourteen recipients (11 males and 3 females) underwent orthotopic heart transplantation with standard immunosuppressive therapy protocols (3 cases) or induction therapy protocols (11 cases). Cyclosporine, azathioprine or mycophenolate mofetil, and prednisolone were applied as the maintenance immunosuppressive regimen. Acute graft rejection episodes occurred within 3 to 6 months in 1 case, within 6 months to 1 year in 3 cases, within 1 to 2 years in 3 cases, within 2 to 5 years in 6 cases, and above 5 years in 1 case.

RESULTSNo significant difference was found in the incidence of late heart rejection between the patients receiving the two immunosuppressive therapy protocols. Immunosuppressants were withdrawn or spared in 8 recipients due to different causes. Nine recipients with steroid-sensitive acute cardiac allograft rejection were treated with steroid-pulse therapy, while the other 5 were treated with a short course of polyclonal antithymocyte antibodies because of steroid-resistant acute rejection; in 11 cases, azathioprine was converted to mycophenolate mofetil. Four of the 5 late deaths occurred in the recipients with steroid-resistant rejection. The surviving recipients had a good quality of life, and no recurrent episodes of rejection or infection were observed in the follow-up period.

CONCLUSIONSLate acute cardiac allograft rejection is associated mainly with patient compliance but not with early immunosuppressive therapy protocols. The episodes are rather severe and should be timely treated with steroid pulses or polyclonal antithymocyte antibodies.

Adolescent ; Adult ; Cyclosporine ; Female ; Graft Rejection ; etiology ; prevention & control ; Heart Transplantation ; adverse effects ; Humans ; Immunosuppression ; methods ; Male ; Middle Aged ; Mycophenolic Acid ; analogs & derivatives ; Young Adult

Child, Preschool ; Cyclophosphamide ; therapeutic use ; Cyclosporine ; therapeutic use ; Female ; Humans ; Infant ; Male ; Mycophenolic Acid ; analogs & derivatives ; therapeutic use ; Nephrotic Syndrome ; complications ; drug therapy ; pathology

This study was purposed to evaluate the curative efficacy of second allogeneic hematopoietic stem cell transplantation (allo-HSCT) after failure of the first allo-HSCT in aplastic anemia patients, the cause of implant failure after allo-HSCT and clinical data of 10 severe aplastic anemia (SAA) patients in the second allo-HSCT were retrospectively analyszed. The second HSCT conditioning programs include: cyclophosphamide (CTX) + fludarabine (FLU)+ anti-thymocyte globulin (ATG) combination chemotherapy for 3 cases; CTX + FLU + white busulfan (Bu) + ATG combination chemotherapy for 7 cases. The prevention regimen of graft-versus-host disease (GVHD) include cyclosporine (CsA), mycophenolate mofetil (MMF) and methotrexate (MTX). The median count of mononuclear cell infusion was 12.17 (5.99-18.12)×10(8)/kg. The CD34(+) cell count was 5.2 (3.8-10.9)×10(6)/kg. The results showed that 10 evaluable patients achieved hematopoietic reconstitution with absolute neutrophil >0.5×10(9)/L, platelets >20×10(9)/L at 15d (8-21d) and 17d (11-27d) after transplantation. The grade I aGVHD occurred in 2 case, grade II in 1 case, chronic GVHD in 3 cases. Transplant-related deaths occurred in 4 cases. The disease-free survival rate, transplant-related mortality, GVHD after transplantation were 60%, 40% and 50% respectively. It is concluded that the second allo-HSCT is an effective therapy for aplastic anemia after allo-HSCT implant failure.
Allografts ; Anemia, Aplastic ; therapy ; Antilymphocyte Serum ; Cyclosporine ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Methotrexate ; Mycophenolic Acid ; analogs & derivatives ; Retrospective Studies