Evaluation Of Cyclosporine Research Articles

Evaluation of cyclosporine 0.05% and artificial tears for the management of dry eye disease following cataract surgery: a randomized controlled trial.

To compare the effects of cyclosporine 0.05% and artificial tears on dry eye disease following cataract surgery. This prospective, double-masked, randomized clinical trial enroled 60 eyes of 60 eligible cataract patients who completed the study. Patients were randomized to receive either cyclosporine 0.05% or artificial tear four times daily for 1 month following cataract surgery. Clinical assessments included refraction, corrected distance visual acuity, tear break-up time (TBUT), Schirmer's test, and the visual analogue scale (VAS). An independent sample t-test was used to compare the means of the variables between the two groups. Mean patient age was 64.15±9.17 (range, 45-90), of which 53% (n=32) were female. There was no significant difference in mean age (P=0.308) between the two groups. One month postoperatively, the cyclosporine 0.05% group had a significantly higher TBUT value (P=0.004). Schirmer's result (P=0.095) and the VAS questionnaire scores (P=0.374) did not show a statistically significant difference between the two groups. There was no significant difference in the visual outcomes (P>0.05). Cyclosporine 0.05% was superior to artificial tears in improving tear stability after cataract surgery in the management of immediate postoperative dry eye. It may provide a more effective therapeutic option for the management of dry eye symptoms in the clinical setting.

Evaluation of Cyclosporine and Tacrolimus Dose Changes During Post-transplantation Period and Their Association with Endomyocardial Biopsy Grading

Background: Changes in the dosage of immunosuppressive drugs following organ transplantation, especially the heart, can be a potential predictor of long-term post-transplant outcomes. It may also be related to the degree of histopathological involvement of endomyocardium. Objectives: We aimed to evaluate cyclosporine and tacrolimus dose changes during post-transplantation biopsies and their association with endomyocardial biopsy grades. Methods: This retrospective study was performed on 100 cardiac transplant patients who underwent endomyocardial biopsies to assess graft stability. In the present study, the patients were divided into two groups receiving cyclosporine (13 cases) and tacrolimus (87 cases). The data was collected by reviewing the recorded files. Results: Regarding the administration of cyclosporine, at different times after biopsy, there was no significant relationship between the plasma level of the drug and the grade of biopsy. Concerning tacrolimus, there was a significant reverse association between serum concentration and biopsy grade at the first biopsy after transplantation (about one month after transplantation), although this relationship was not observed in the subsequent steps of biopsy. Also, the Quilty effect frequency was not significantly associated with biopsy grade in different biopsies for both drugs. Conclusions: There is a lack of association between endocardial biopsy grade in the heart and the serum level of cyclosporine after transplantation. However there is a significant reverse relationship between endomyocardial biopsy grade and serum Tacrolimus concentration in the first weeks after transplantation and thus monitoring serum Tacrolimus after transplantation may play an important role in predicting acute rejection.

Optimization and evaluation of cyclosporine A nanosuspension stabilized by combination stabilizers using high pressure homogenization method

Optimization and evaluation of cyclosporine A nanosuspension stabilized by combination stabilizers using high pressure homogenization method

The cyclosporine transdermal transfer possibility study on model systems

Aim: to develop the emulsion transdermal therapeutic system (TTS) of cyclosporine and the research of its diffusion from TTS.Materials and methods. The quantitative evaluation of cyclosporine in model media was performed on liquid chromatograph Agilent 1100 G1311 with spectrophotometric detector G1315B (Germany). For the production of the emulsion matrix, the Heidolph DIAX900 disperser (Germany) and the ultrasonic homogenizer Hielscher UIS250V (Germany) were used. The cyclosporine diffusion from TTS through Strat-M membrane (25 mm in diameter, Merck Millipore) was studied using Copley diffusion analyser (Great Britain).Results. Using the developed method of micro-HPLC, it was established that the amount of cyclosporine passed through the Strat-M membrane over 24 hours from 10 sm2 TTS, containing 173 mg of the substance, was 5.9 mg. The estimated blood concentration is ~ 50 ng/ml which corresponds to the therapeutic maintenance blood concentration during organ transplantation (50–75 ng/ml).Conclusion. The model studies demonstrate the possibility of the cyclosporine transdermal transfer.

Evaluation of Cyclosporine A with β-TCP in the Treatment of Human Infra bony Defects - A Randomized Controlled Pilot Study.

Cyclosporine A (CsA), an immunosuppressant, is considered a life saver drug in organ transplant cases. It has also been tested in animal and human studies for periodontal applications as it selectively inhibits T lymphocyte proliferation, Interleukin-2 (IL-2) and other cytokine production, without any effect on T suppressor cells, thereby suppressing the cell mediated immunity and suppressing the inflammation. Inflammatory and immunological responses have been found to be decreased and bone formation is found to be increased in immunosuppressed animals. CsA is also supposed to potentiate osseous regeneration due to increase in the bone alkaline phosphatase levels and a direct activating effect on osteoblasts. The present study was aimed at evaluating locally administered low dose of CsA which is potent immunosuppressant along with β-Tricalcium phosphate (β-TCP) in comparison with β TCP alone, in the treatment of human infrabony defects, over a period of six months. Thirty two systemically healthy chronic periodontitis patients with infrabony defects were included in the randomized, controlled, parallel arm study and were allocated into either Group A (n =16), patients treated with β-TCP + CsA (2 mg) or Group B (n =16), patients treated with β-TCP. Clinical parameters [Relative Attachment Level (RAL), Probing Depth (PD), Gingival Recession (GR)] and radiographic parameters were measured at baseline and six months postoperatively. Statistical analysis was done using SPSS version 16 software. Student's paired and independent t-test were used for intra and inter-group analysis. Both Group A and Group B showed statistically significant improvements in clinical and radiographic parameters from base line to six months post-operatively. The Clinical Attachment Level (CAL) gain, Linear Bone Growth (LBG) and Percentage Bone Fill (% BF) were 2.38±1.12 mm, 1.90±1.48 mm and 49.83±29.23 mm in Group A and 2.57±1.22 mm, 2.03±1.16 mm and 62.84±29.70 mm in Group B respectively, inter group comparison showed no statistically significant difference. Both the groups revealed statistically significant improvement in clinical and radiographic parameters and adjunctive use of CsA did not prove beneficial.

Evaluation of cyclosporine a as a cardio- and neuroprotective agent after cardiopulmonary resuscitation in a rat model.

The immunosuppressant drug cyclosporine A (CsA) is a direct inhibitor of the mitochondrial permeability transition pore, which is the common end point of many pathways of ischemic preconditioning and postconditioning. We studied the neuroprotective and cardioprotective effect of CsA after cardiac arrest (CA) in a rat model of cardiopulmonary resuscitation. After institutional approval by the Governmental Animal Care Committee, 83 rats were subjected to 6 min of CA and were randomly and investigator-blinded allocated either to placebo (n = 15) or interventional group (n = 15; 10-mg/kg body weight CsA intravenously) after restoration of spontaneous circulation (ROSC). Before CA (baseline) as well as 1 h and 3 h after ROSC, continuous measurement of stroke volume, left ventricular ejection fraction, preload adjusted maximum power, and end diastolic volume was performed using a conductance catheter. One day, 3 days, and 7 days after ROSC, neurological outcome was evaluated by a tape removal test. After 7 days of reperfusion, coronal brain sections were analyzed by counting Nissl-positive (i.e., viable) neurons and terminal deoxynucleotidyl transferase dUTP nick end labeling positive (i.e., apoptotic) cells. Animals treated with CsA had a higher stroke volume (96 [93; 107] μL vs. 78 [73; 94] μL; P = 0.02), higher ejection fraction (58% [51%; 63%] vs. 42% [35%; 51%]; P = 0.002), and higher preload adjusted maximum power (4.8 [3.9; 6.1] vs. 2.3 [2.0; 2.6] mW/μL; P < 0.001). End diastolic volume remained stable in the CsA group 3 h after ROSC in comparison to baseline (160 [143; 181] μL vs. 157 [148; 192] μL; P = 0.56), whereas it increased in the placebo group (169 [153; 221] μL vs. 156 [138; 166] μL, P = 0.05). More neurons survived after administration of CsA (2.5 [1.6; 4.9] vs. 0.7 [0.4; 1.4]; P = 0.005). Compared to placebo-treated animals, the time in the tape removal test 7 days after ROSC was reduced by half in the CsA group without reaching statistical significance (26 [22; 51] vs. placebo 53 [38; 56] s; P = 0.13). Cyclosporine A treatment neither affected the number of terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells nor the survival rate. Pharmacological postconditioning with CsA after successful cardiopulmonary resuscitation attenuates myocardial dysfunction and reduces neuronal damage.

Formulation and evaluation of Cyclosporin A emulgel for ocular delivery

Emulgels have been extensively covered as a promising drug delivery system for the administration of lipophilic drugs. This work was conducted to develop an emulgel formulation for Cyclosporin A (CsA) employing polycarbophil as the gelling agent for ocular delivery. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, stability, precorneal clearance and irritation. Results showed that CsA emulgel formulations prepared with polycarbophil exhibited acceptable physical properties and drug release, which remained consistent after storage for 3 months. A prolonged retention time was also observed on the ocular surface with improved ocular bioavailability and no irritation. Therefore, the polycarbophil-based emulgel could be exploited as a potential hydrophobic drug carrier for topical ocular drug delivery.

Evaluation of cyclosporine A eye penetration after administration of liposomal or conventional forms in animal model

A lot of researches have investigated the effects of topical cyclosporine A on the eye surface layers’ diseases. By now the main limitation in cyclosporine application is the low permeation of the drug into the posterior segments of the eye. The aim of present study was to formulate high permeable dosage form can be beneficial in the topical treatment of the uveitis. To reach higher corneal drug absorption and drug concentration in the posterior segments of the eye, 3 nanoliposomal formulations containing 0.5 mg/ml cyclosporine A were prepared. Liposomal formulations and the commercial product (Restasis®) were instilled in the right and left eyes of the rabbits, respectively. The rabbits were killed in the 3, 7, 14 and 28 days of study and the aqueous humor and vitreous were extracted. Mean size of liposomal formulation number 1, number 2 and number 3 were 107.2 ± 0.7, 129.3±0.9 and 144.8±1.8 nm and their zeta potential were -5.0±1.7, -5.5±2.3 and 44.6±6.2 mV, respectively. Results of ocular analysis showed that the liposomal formulations could increase the concentration of the drug in the aqueous and vitreous like Restasis®. But, in contrast with what has been expected the findings of this study implicate nanoliposomal formulations prepared could not make a significant difference in concentration of the drug in aqueous and vitreous humor compared to Restasis® (anionic microemulsion). In conclusion, we can state that liposomes with the same composition as our formulations are not more efficient than microemulsion for cyclosporine as ophthalmic drug delivery.

Comparative evaluation of cyclosporine A/HPβCD-incorporated PLGA nanoparticles for development of effective ocular preparations

To improve poor water solubility of cyclosporine A (CsA), hydroxypropyl-beta-cyclodextrin (HPβCD) was incorporated into the nanoparticle formulation. Solid complexes of CsA with HPβCD in different ratios were prepared by the kneading method. CsA containing alone or in combination with HPβCD in poly-lactide-co-glycolide (P-CsA or P-CsA-HPβCD) nanoparticles were prepared by the emulsification solvent evaporation method. The mean size of CsA-loaded NPs was found to be approximately 220 nm. The solubility of CsA was significantly improved and the phase solubility diagram of CsA–HPβCD systems showed an AL type phase. Nanoparticles showed high CsA encapsulation efficiency (88%) and production yield (89%). Release rate was increased by the presence of HPβCD and total cumulative release ranged from 75% to 96% in 24 h. In vitro cytotoxicity study assay resulted in a low toxicity for all types of nanoparticles. After 6 h incubation period, the cellular uptake was found at 33% and 32% for P–CsA and P–HPβCD–CsA nanoparticles, respectively.

Evaluation of cyclosporine A in a stroke model in the immature rat brain

The effects of ischemia–reperfusion on opening of the mitochondrial permeability transition pore (mPTP) and its blockade in the immature brain are not fully understood. Presently, we evaluated the effect of cyclosporine A (CsA) on cell death and mPTP opening in a model of transient focal ischemia induced by permanent left middle cerebral artery, and homolateral transient common carotid artery occlusion (50min) in P7 rats. CsA (10mg/kg) was administered 14h before induction of ischemia and effects were analyzed at 30–40min and 48h after reperfusion. CsA administration reduced infarct size, DNA fragmentation and apoptotic bodies, and inflammatory responses in mild but not severe injury. CsA increased the Ca2+ load required to open the mPTP (78.4±19.2 vs. 50.2±19.9nmol.mg−1 protein, p<0.05) in limiting the decoupling of the respiratory chain by unchanged state 3 but reduced state 4, and attenuated early calpain-mediated alpha-spectrin proteolysis. In conclusion, CsA mediates inhibition of mPTP opening and has a tendency to protect immature rat brain against mild ischemic injury. This article is part of a Special Issue entitled "Interaction between repair, disease, & inflammation."

Long‐term evaluation of cyclosporine and tacrolimus based immunosuppression in pediatric liver transplantation

Both calcineurin inhibitors (CNIs), cyclosporine and tacrolimus, are widely used in pediatric liver transplant recipients and currently data are limited with regards to long-term results using the one drug or the other in comparable low doses. We conducted the present study to assess the advantages and disadvantages of both drugs in children at least five yr post-liver transplantation. A total of 129 children were enrolled in the study. Thirty-eight of the children were switched to tacrolimus monotherapy for different reasons [steroid resistant graft rejection (n = 15), chronic rejection (n = 5), severe acute rejection (n = 4), repetitive acute graft rejection (n = 5), dysfunction of the transplant (n = 3), insufficient CsA metabolism (n = 3), hypertrichosis (n = 2), and CsA toxicity (n = 1)], four patients had primary tacrolimus therapy, and 87 patients are receiving cyclosporine. Mean trough levels were 5.3 +/- 2.3 ng/mL (tacrolimus) and 73.6 +/- 44.5 micro/L (cyclosporine), respectively at least five yr post-orthotopic liver transplantation (OLT). There was no significant difference in the calculated glomerular filtration rate between children on cyclosporine and tacrolimus (142.7 + 39.5 mL/min/1.73 m(2) vs. 151.1 +/- 44.1 mL/min/1.73 m(2)). The incidence of arterial hypertension was 7.1% vs. 9.2%, that of hepatotoxicity was 0% vs. 2.3%. Cosmetic changes were found in more than one-third of the patients on cyclosporine and in 4.8% of the patients receiving tacrolimus. Quality of life was excellent in both groups (self assessment). The impact of CNIs on chronic graft dysfunction cannot be assessed by our present study. We conclude from the results that cyclosporine and tacrolimus are both excellent drugs for maintenance immunosuppression in the long-term course following pediatric liver transplantation. However, this retrospective analysis is limited by the bias between children on CsA as compared with patients receiving tacrolimus. A prospective randomized controlled trial is needed in order to assess which CNI is the best for children following OLT.

Evaluation of cyclosporin (CsA) profiles month 2 to 6 in an international phase III randomized, multicenter, double-blind study of everolimus in DE novo heart transplant recipients

heart is not available. A large amount of experience exists with BTT in the adult population; relatively less information is available in the pediatric population with pulsatile devices. Ten pediatric patients are presented who underwent BTT or recovery with pneumatic paracorporeal systems. The Berlin Heart biventricular assist device was utilized in 1 patient (BVAD), the Medos VAD was utilized in four patients (1 LVAD, 3 BVAD); the Thoratec VAD in 5 patients (3 BVAD, 2 LVAD). The pediatric population consisted of 3 females and 7 males. Mean age of the population was 7.4 years (youngest 4 months), weight 25 kg, BSA 0.88 m. Etiologies for heart failure were: 4 viral, 3 congenital and 3 idiopathic cardiomyopathies. Prior to implant, all patients exhibited evidence of progressive cardiac failure despite inotropic support, 2 patients had been on ECMO for 1 week. Mean duration on the device was 34.3 (8 -107) days. Two patients suffered strokes and recovered without sequelae. Two patients died of ischemic strokes and 1 of sepsis. Seven patients survived (6 transplanted and 1 weaned) for a survival rate of 70% compared to survival for ECMO as BTT of 40–50%. All survivors experienced complications related to bleeding, thromboembolic events, and infections. The Thoratec VAD can be placed in small patients with large hearts that can accommodate the available cannulas. The Berlin Heart and the Medos VAD have a selection of ventricles with small stroke volumes. All 3 systems can be successfully used in the pediatric population as BTT with better survival than ECMO. Anticoagulation in children and selection criteria has to be better understood. Lack of potential donors may further accelerate the use of these devices.

Evaluation of cyclosporine C 2 levels in long-term stable renal allograft recipients

Background The use of cyclosporine was traditionally monitored by the trough level (C 0). However, the immunosuppressive effects of cyclosporine correlate with its drug exposure, represented by the area under curve (AUC). It was also noted that cyclosporine C 0 level correlated with AUC poorly, while C 2 level (concentration at 2 hours after drug administration) satisfactorily correlated with AUC. Most recent studies concern the use of C 2 levels in de novo renal transplant patients; target levels of C 2 have been suggested. There is rare discussion about the C 2 target level for long-term cyclosporine-maintenance patients. Our objectives were to analyze the cyclosporine C 2 levels of patients more than 12 months after transplantation as well as changes in C 2 with time and the correlation between C 2 level and renal function. Methods and patients This was a cross-sectional case-controlled study of 101 kidney recipients immunosuppressed with a cyclosporine-based regimen for at least 12 months. Both C 0 and C 2 levels were examined at various time points during outpatient clinic follow-up. The patients were stratified according to the time after transplant surgery, or to their renal function. Results The 101 patients were divided into three groups based on the time after renal transplant surgery. Groups 1, 2, and 3 represented patients transplanted for 1 to 3 years ( n = 16), 4 to 6 years ( n = 35), and more than 6 years ( n = 50), respectively. The C 2 levels for each group were 657 ± 232, 561 ± 186, and 580 ± 243 ng/mL, respectively, ( P = NS). When stratified into low versus high C 2 groups, there were no significant differences in renal function both at the beginning and at the end of 1 year follow-up. Seven of 67 patients shifted to stronger immunosuppression in the low C 2 group, but only 2/34 in the high C 2 group, a difference that was not significant ( P = .234 by Fisher Exact Test). Patients with creatinine levels greater than 1.5 mg/dL or lower than 1.5 mg/dL showed no difference in C 2 on C 0 levels. Patients with deterioration of renal function during this period had no different C 2 levels as those with no deterioration of renal function. Conclusion The average C 2 levels among long-term cyclosporine-maintained patients were significantly lower than those previously suggested. C 2 levels did not correlate with the long-term outcome of renal function in patients at least 1 year after renal transplantation.