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 assess the effect of cyclosporine A (CsA) loaded in chitosan conduit on bridging the sciatic nerve defects in a rat model.

METHODSA 10 mm sciatic nerve defect was bridged using a chitosan conduit filled with 10 μl carrier-drug dilution (10 μg/L CsA). In control group, the conduit was filled with the same volume of carrier dilution alone. The regene-rated fibers were studied 4, 8 and 12 weeks after surgery.

RESULTSThe functional study confirmed faster recovery of the regenerated axons in treatment group than control group (P<0.05). There was statistically significant difference of the gastrocnemius muscle weight ratios between treatment and control groups (P<0.05). Morphometric indices of regenerated fibers showed that the number and diameter of the myelinated fibers in CsA-treated animals were significantly higher than those in control group. In immunohistochemistry, the location of reactions to S-100 in CsA group was clearly more positive than control group.

CONCLUSIONCsA loaded in a chitosan conduit results in improvement of functional recovery and quantitative morphometric indices of sciatic nerve. It is easily available without any complications compared with its systemic administration.

Animals ; Chitosan ; Cyclosporine ; administration & dosage ; pharmacology ; Immunohistochemistry ; Nerve Regeneration ; drug effects ; Rats ; Sciatic Nerve ; chemistry ; injuries

AIMTo develop a less toxic alternative for sandimmun neoral (Neoral). To study the preparation conditions and to compare its pharmacokinetic characteristics with Neoral.

METHODSPolylactide nanoparticles loaded cyclosporine A was prepared by solvent-nonsolvent method. Polylactide nanoparticles were administered by oral in a dosage of 15 mg.kg-1. The CyA concentration in whole blood sample was determined by HPLC.

RESULTSThe quantities of CyA, PLA and volume of acetone added had significant influence on the NP diameters. Under proper condition, the nanoparticles with diameters of 57.5 nm were obtained. The relative bioavailability in rats was 101.6%, with a smaller absorption rate (P < 0.05) and a smaller elimination rate (P < 0.1).

CONCLUSIONThe nanoparticles (diamater < 100 nm) with relative high bioavailability were prepared using solvent-nonsolvent method. It is suitable for further study.

Administration, Oral ; Animals ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Delayed-Action Preparations ; Immunosuppressive Agents ; administration & dosage ; pharmacokinetics ; Male ; Nanotechnology ; Polyesters ; Random Allocation ; Rats ; Rats, Wistar

OBJECTIVEAplastic anemia is characterized by bone marrow failure and marked reduction of white blood cells, red blood cells and platelets in peripheral blood. Clinical studies have shown that immunosuppressive therapy greatly prolonged the long-term survival of some patients with aplastic anemia. But in severe aplastic anemia (SAA) patients whose ANC was < 0.5 x 10(9)/L, platelets were < 20 x 10(9)/L, very low bone marrow proliferation and high death rate were observed. The present study aimed to evaluate the efficacy of immunosuppressive treatments with cyclosporine A (CSA) alone or CSA combined with antithymocyte globin (ATG) in children with acquired SAA.

METHODSFifty-four cases with SAA were treated with immunosuppressive agents mentioned above in our department from Jan. 1997 to June 2003, 31 of the cases had treated with CSA combined with ATG. There were 18 cases with SAA type I and 13 cases with SAA type II in CSA combined with ATG group, and 13 cases had very severe aplastic anemia. The other 23 cases were treated with CSA alone (CSA group), 10 of these cases had SAA-I and 13 had SAA-II, and 5 cases had very severe aplastic anemia. The responsive rate, relapse, adverse reactions and event free survival (EFS) were compared between CSA combined with ATG group and CSA group.

RESULTSThe proportions of patients with different types of the disease and severity were comparable between the two groups. The responsive time of the CSA combined with ATG group and CSA group was 2.5 months and 3.5 months, respectively (P < 0.05), the responsive rate in two groups was 81% (25/31) and 52% (12/23), respectively (chi(2) = 4.962, P < 0.05). In 37 cases who were responsive to therapy, the relapse rate was 8% (2/25) and 50% (6/12) respectively (chi(C)(2) = 6.143, P < 0.05). There were no significant differences in adverse reactions to the immunosuppressive agents. All cases were followed-up for more than 1 year, and the event-free survival over one year in these two groups was 81% (25/31) and 52% (12/23), respectively. Forty-seven cases were followed-up for more than two years, and the event-free survival was 74% (20/27) and 50% (10/20), respectively (P < 0.01). Twelve cases were followed-up for over 5 years. There were no secondary tumor, myelodysplastic syndrome and other colony diseases.

CONCLUSIONThe immunosuppressive therapies for acquired severe aplastic anemia in childhood were effective. The effect of CSA combined with ATG was better than that of CSA alone, and the relapse rate was lower with the combined treatment. However, the long-term effect needs longer follow-up studies to evaluate.

Adolescent ; Anemia, Aplastic ; drug therapy ; Antilymphocyte Serum ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; therapeutic use ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Male

INTRODUCTIONWhile corticosteroids are an effective choice of treatment for severe vernal keratoconjunctivitis (VKC), their long-term use is restricted due to side effects. This study was conducted to evaluate the efficacy and safety of topical cyclosporine A (CsA) 0.05% in the treatment of VKC.

METHODSA total of 30 patients with VKC that was resistant to topical corticosteroids, antihistamines and mast cell stabilisers were treated with topical CsA 0.05%. Patients were evaluated at Weeks 4, 8 and 12 after the initiation of therapy. Symptoms and signs observed before and after treatment were recorded and scores were assigned. Scores for symptoms and signs, the need for topical corticosteroids and ocular side effects were evaluated.

RESULTSAt baseline, the median values of the symptom and sign scores were 10.0 (range 5.0-18.0) and 6.0 (range 2.0-13.0), respectively. At Week 4 of treatment with topical CsA 0.05%, the median values of the symptom and sign scores were 3.0 (range 0-14.0) and 3.0 (range 0-8.0), respectively. The reductions in the symptom and sign scores were statistically significant. The reduction in the need for corticosteroid was statistically significant by Week 12 of therapy. No significant side effects were reported.

CONCLUSIONTopical CsA 0.05%, which can help to reduce corticosteroid usage, is an effective and safe alternative for the treatment of resistant VKC. Further studies are needed to determine the optimal duration of therapy and possibility of recurrence.

Administration, Topical ; Adolescent ; Adrenal Cortex Hormones ; administration & dosage ; Adult ; Child ; Cohort Studies ; Conjunctivitis, Allergic ; drug therapy ; Cornea ; drug effects ; Cyclosporine ; administration & dosage ; Drug Administration Schedule ; Eye ; drug effects ; Female ; Humans ; Immunosuppressive Agents ; administration & dosage ; Male ; Recurrence ; Young Adult

OBJECTIVETo test the immunosuppressive effect of cyclosporine (Cs) in a polymer placed in the anterior chamber of corneal allograft recipients.

METHODSWistar inbred rats with vascularized corneas were recipients of corneal allografts from Sprague-Dawley donor rats. Rats underwent penetrating keratoplasty and were divided randomly into four groups: untreated control animals (UCA); Cs-polymer anterior chamber recipients (CPA); co-polymer subconjunctival recipients (CPS); and Cs-olive oil drop recipients (COO). Grafts were examined by slit lamp every 3 days and clinical conditions were scored. Cs concentration in the aqueous humor was assayed at 1, 2, and 4 weeks. At 1, 2 and 4 weeks after transplantation, the operated eyes were collected for histopathological evaluation of the grafts.

RESULTSThe median survival time of the allografts was 8.2 +/- 1.48 days for the UCA group, 11.4 +/- 2.50 days for the CPS group, and 17.0 +/- 2.00 days for the CPA group. There was a statistically significant difference (P < 0.05) between survival time of the allografts in the animals of the CPA group compared to the other groups of graft recipients. Significantly higher concentrations of Cs were found in the eyes given an anterior chamber implant of Cs-polymer, compared to other treatment groups or untreated rats. A transient inflammatory response in the anterior chamber was observed in the CPA group.

CONCLUSIONSCs-polymer placed in the anterior chamber significantly prolongs corneal allograft survival time in a high risk corneal graft rejection model. This intraocular delivery system may be a valuable adjunct for the suppression of immune graft rejection.

Animals ; Aqueous Humor ; metabolism ; Corneal Transplantation ; Cyclosporine ; administration & dosage ; metabolism ; Drug Delivery Systems ; Graft Survival ; Immunosuppressive Agents ; administration & dosage ; Male ; Rats ; Rats, Wistar ; Transplantation, Homologous

OBJECTIVETo evaluate the therapeutic effects of a combined immunotherapy, high-dose immunoglobulin (HDIG) plus cyclosporine A (CsA) plus prednisone (P), in children with aplastic anemia (AA) and to explore the association of peripheral blood lymphocyte subsets, peripheral blood cells and marrow CD34+ cells with therapeutic effects in AA.

METHODSThe clinical data of 46 children with AA and who received the combined immunotherapy of HDIG + CsA + P were retrospectively studied.

RESULTSOf the 46 children with AA, 31 (67.4%) were responded to the combined immunotherapy. The binary logistic regression analysis showed low absolute neutrophil count (B=4.703, p<0.05), low percentage of peripheral blood CD4+ cells (B=0.142, p<0.05) and low ratio of peripheral blood CD4+/CD8+ (B=2.945, p<0.05)were associated with poor therapeutic effects. The ratio of CD34+/karyocytes of bone marrow in children with AA was lower than that in normal individuals, but it was not significantly related to the therapeutic effect.

CONCLUSIONSThe combined immunotherapy (HDIG+CsA+P) was effective in children with AA. The absolute neutrophilcount, the percentage of peripheral blood CD4+ and the ratio of peripheral blood CD4+/CD8+ were important prognostic factors in AA.

Adolescent ; Anemia, Aplastic ; drug therapy ; immunology ; CD4-CD8 Ratio ; Child ; Child, Preschool ; Cyclosporine ; administration & dosage ; Female ; Humans ; Immunoglobulins ; administration & dosage ; Infant ; Logistic Models ; Male ; Retrospective Studies

To explore the treatment of refractory anemia (RA), 7 cases of myelodysplastic syndrome (subtype of refractory anemia) were treated in combination of cyclosporin A (CsA) with stanozolol. Duration of treatment with CsA was 5 months-3 years (mean 13 months). The results showed that among 7 cases 6 were effective, 1 case no responded to treatment. 3 cases out of 6 effective cases achieved complete remission without transfusion dependence, 1 cases achieved partial remission, 2 cases were improved. During the investigation signs of leukemia ot other malignant tumors not were found in all cases. In conclusion, CsA treatment is effective for part cases of RA, side effects of drugs are tolerable for patients.
Adolescent ; Adult ; Aged ; Anemia, Refractory ; drug therapy ; Cyclosporine ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Male ; Middle Aged ; Stanozolol ; administration & dosage

OBJECTIVETo investigate retrospectively the efficacy of cyclosporine A (CsA) in the treatment of membranous lupus nephropathy (MLN).

METHODSTwenty-four patients with systemic lupus erythematosus (SLE) and biopsy-proven MLN were treated with CsA in combination with prednisone. CsA was given at a starting dosage of 5 mg x kg(-1) x d(-1) for 3 months, with a 1 mg x kg(-1) x d(-1) reduction every month and then maintained at a dosage of 2 mg x kg(-1) x d(-1). The dosage of oral prednisone differed from person to person according to levels of extra-renal activity. Clinical efficacy and adverse reactions were retrospectively analyzed. Complete remission was defined as having a urinary proteinuria level (Upr) of < 0.4 g/d, and normal serum albumin and serum creatinine (SCr) levels, without SLE activity. Partial remission was defined as having a UPr decrement > 50% of baseline value and a serum albumin value of 30 - 35 g/L, without SLE activity. No response was defined as having a Upr decrement < 50% of baseline value and > 2.0 g/d, or as a deterioration of renal function, or as having active SLE.

RESULTSOne patient could no longer undergo follow-up, and the other 23 patients were treated with CsA and followed up for 6 - 36 months (mean 16.8 +/- 8.4 months). The mean starting dosage of CsA was 4.7 +/- 0.5) mg x kg(-1) x d(-1) and the trough level of the whole blood CsA was 248 +/- 110) micro g/L. Twelve patients (52.2%) achieved complete remission, 10 patients (43.3%) achieved partial remission after CsA treatment, and one patient showed no response. At different CsA treatment timepoint, the complete remission rates were 17.4% (3rd month), 21.7% (6th month), 40% (12th month), 88.9% (18th month) and 100% (24th month) respectively. SCr elevation, when within a normal limit was not observed in most patients during early CsA administration, and at the end of the follow-up all the patients had a normal SCr. Relapse occurred in 33.3% of the patients after withdrawing CsA for 4 - 24 months. No chronic CsA renal toxicity was observed in 4 patients who had a repeat renal biopsy after CsA treatment for 6 - 24 months.

CONCLUSIONSCsA could be regarded as an effective therapy for patients with membranous lupus nephropathy, but its adverse effects, especially its nephrotoxicity, should be carefully monitored during CsA treatment.

Adolescent ; Adult ; Cyclosporine ; administration & dosage ; therapeutic use ; Female ; Glomerulonephritis, Membranous ; drug therapy ; Humans ; Lupus Nephritis ; drug therapy ; Male ; Prednisone ; administration & dosage ; Retrospective Studies ; Treatment Outcome

AIMTo study the preparation conditions and its oral pharmacokinetic characteristics of cyclosporine A (CyA) pH sensitive nanoparticles.

METHODSThe CyA pH sensitive nanoparticles were prepared by the quasi-emulsion solvent diffusion technique (QESD). Male Sprague-Dawley (SD) rats weighing (250 +/- 20) g were selected and randomly divided into five groups. The bioavailability of CyA from nanoparticles and Neoral microemulsion were assessed at a dose of 15 mg x kg(-1) by gavage. The concentration of CyA in whole blood samples was detected by HPLC to evaluate the relative bioavailability of CyA pH sensitive nanoparticles.

RESULTSThe blood concentration profiles of CyA pH sensitive nanoparticles in rats fitted to two compartment models using 3P87 pharmacokinetic calculation program. Compared with the Neoral microemulsion, the relative bioavailability of CyA was 94.8%, 115.2%, 113.6% and 132.5% for CyA-E100, CyA-L100, CyA-L100-55 and CyA-S100 nanoparticles respectively.

CONCLUSIONCyA-S100 nanoparticles was shown to significantly improve the oral bioavailability of CyA compared with Neoral microemulsion (P < 0.05). While there were no significant differences between Neoral microemulsion and other CyA pH sensitive nanoparticles. With these results, the potential of pH-sensitive nanoparticles for the oral delivery of CyA was confirmed. Furthermore, this formulation approach can be used to improve the oral bioavailability of other poorly soluble and poorly absorbable drugs.

Administration, Oral ; Animals ; Area Under Curve ; Biological Availability ; Cyclosporine ; administration & dosage ; pharmacokinetics ; Hydrogen-Ion Concentration ; Male ; Nanostructures ; Random Allocation ; Rats ; Rats, Sprague-Dawley