A Randomized, Prospective Multicenter Pharmacoepidemiologic Study of Cyclosporine Microemulsion in Stable Renal Graft Recipients1,2,3

Keown, Paul; Landsberg, David; Halloran, Philip F.; Shoker, Ahmed; Rush, D.; Jeffery, John; Russell, David; Stiller, C; Muirhead, Norman; Cole, Edward; Paul, Leen; Zaltzman, Jeffrey S.; Loertscher, Rolf; Daloze, P; Dandavino, R; Boucher, Anne; Handa, Paul; Lawen, Joseph; Belitsky, P; Parfrey, Patrick

doi:10.1097/00007890-199612270-00009

Cited by 195 publications

(57 citation statements)

References 12 publications

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“…Studies performed early after transplantation and also in stable patients, in different types of organ transplantation, have consistently shown improved dose-concentration linearity, reduced between-subject and within-subject variability, stronger concentration-AUC correlations and an improved efficacy/toxicity/tolerability profile [3,14,17,21,22,23,37,38,431. Compared with the oil-based formulation, the higher Cmax and AUC achieved with the microemulsion formulation [7] provide higher exposure, which has been associated with reduced, but still significant, acute rejection rates of 35% in patients receiving cyclosporine, azathioprine, and prednisone [21, 411. Concurrently, many studies have been performed to perfect therapeutic cyclosporine monitoring after transplantation [7,9,10,35,401.…”

Section: Introductionmentioning

confidence: 99%

Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations

et al. 2003

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This study analyzed early changes in trough blood cyclosporine concentrations and cyclosporine exposures after kidney transplantation. Seventy-two patients who received cyclosporine-based immunosuppressive therapy were intensively monitored (CO) during the first 6 months after transplantation. Full pharmacokinetic studies were performed at day 4, and months 2, 3, and 6 after transplantation. Mean steady-state, dose-adjusted trough cyclosporine blood concentrations increased from 1.1 f 0.60 (day 7) to 2.0 i 1.20 ng/ml per mg (day 30, P < 0.01). Steadystate, dose-adjusted cyclosporine exposure parameters (CO, Cmax, AUC, Cavg, and Cl2) were significantly lower at day 4 than at months 2, 3, and 6 after transplantation (P < 0.01). Initial cyclosporine doses produced target concentrations in only 30% of the patients at day 3. C2 was the single concentration that showed high and consistent correlation with serial AUC measurements (y2 2 0.76). The incidence of biopsy-proven acute rejection was 20.5% and was not associated with ethnicity, HLA mismatch, adjunctive therapy, or blood trough cyclosporine concentrations below 200 ng/ml at day 3. Significant time-dependent increases in steadystate cyclosporine exposure occur during the first month after kidney transplantation. Due to the low relative bioavailability early after surgery, higher doses and more frequent cyclosporine dose adjustments are necessary to produce target exposures early after transplantation.

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Section: Introductionmentioning

confidence: 99%

Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations

et al. 2003

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“…Some study concluded that it's better to start absorption profiling to prevent any nephrotoxicity and It declared that the mixture of C0 and C2 (C2/C0 or CA) provided good correlation with AUC 0-12 (70). However, literatures in this field are rare and seems that Pharmacodynamics policies and Prospective Randomized clinical trials is needed to be designed to address this question.…”

Section: Relative Importance Of Attaining Cyclosporine Absorptionmentioning

confidence: 99%

A Systematic Review about an Advance in Cyclosporine Monitoring in Kidney Transplant Recipients

Einollahi

Teimoori

2017

Nephro-Urol Mon

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Context: An immunosuppressive drug, Cyclosporine (CsA), has been commonly used in kidney transplants. A safe dosing of CsA often causes nephrotoxity, bone marrow toxicity, and infection. Pharmacokinetic characteristics of CsA and CsA marker relation to the immune suppression have not been completely described in clinical practices yet. Objectives: This review summarizes our achievements on pharmacokinetic and CsA level Marker in kidney transplant patients. Search methods and Selection criteria: A literature review was done using the National Center for Biotechnology Information's Pubmed Medline, Ovid Medline and Embase, and Iranian registries (Iranmedex, SID, MagIran, and IranDoc). Titles and abstracts were then reviewed to select studies based upon the predefined inclusion criteria. Our study defined a population of adult solid organ transplant recipients receiving the cyclosporine that Cyclosporine monitoring was done. Data Collection and Analysis: Two reviewers independently appraised the quality of each trial and extracted the data from the included trials. Results: CsA pharmacokinetics is very different between kidney transplant recipients, in order to CsA profiling, no pharmacodynamic tools has been confirmed yet in clinical practices and the best way to individualize calcineurin inhibitor therapy is still a controversial issue. C0 levels do not exactly predict the CsA level or rejection risk, patient monitored by C2 levels have upper doses of CsA and have a lower frequency of early acute allograft rejection than patients profiled with C0 and although CA is highly heterogeneous closely post-transplant and seems to be unhelpful early after post-transplant it is more favorable after first months after. Conclusions: Establishing a biological CsA marker may be helpful in clinical decisions on the dose. It seemed to be logical that we should re-inspect the possibility of using them as a supplementary tool towards better therapeutic drug monitoring of cyclosporine or it needs to be reevaluated and needs to find a new target for a therapeutic plan in kidney transplant patients.

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“…The current knowledge on cyclosporine pharmacogenetics comes from studies in recipients of solid organ transplants. Bioavailability and clearance of the drug are inluenced by polymorphic P-glycoprotein (ABCB1) in gastrointestinal tract and CYP3A4 and CYP3A5 in the liver, suggesting that these polymorphisms could also inluence the response to cyclosporine treatment in psoriatic patients [27,28]. There was only one pharmacogenetic study performed on psoriasis patients treated with cyclosporine, and it focused only on ABCB1 polymorphisms ( Table 2).…”

Section: Cyclosporinementioning

confidence: 99%

Pharmacogenetics of Psoriasis Treatment

Redenšek¹,

Dolžan²

2017

An Interdisciplinary Approach to Psoriasis

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Psoriasis is a chronic systemic, immune-mediated disorder of unknown aetiology, usually presenting with typical inlammatory skin lesions and/or joint manifestations, but systemic inlammation that may lead to the development of co-morbidities may also be present. First-line therapy encompasses local cutaneous treatment and phototherapy, but with more severe symptoms or systemic course, systemic treatment with methotrexate (MTX), immunosuppressant cyclosporine, retinoid acitretin or biologicals may be used. Treatment response varies between patients in terms of eicacy and/or toxicity, which could, among other reasons, be due to genetic diferences between patients. Approximately 10-30% of patients experience adverse drug reactions with MTX treatment, leading to discontinuation of MTX mostly due to hepatotoxicity. Around 15% of patients experience adverse events when treated with biologicals; however, the most frequent reason for discontinuation is ineicacy or loss of the initially favourable response over time. Ineicacy or occurrence of adverse drug reactions cannot be predicted, so genetic biomarkers of drug response in combination with clinical data could be helpful in treatment planning. Several polymorphic genes have already been associated with treatment outcome, most of them involved in drug metabolism, transport and target pathways. Genetic biomarkers could be helpful in personalized care of psoriasis patients in order to prevent adverse events or predict ineicacy of a certain drug.

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A Randomized, Prospective Multicenter Pharmacoepidemiologic Study of Cyclosporine Microemulsion in Stable Renal Graft Recipients1,2,3

Cited by 195 publications

References 12 publications

Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations

Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations

A Systematic Review about an Advance in Cyclosporine Monitoring in Kidney Transplant Recipients

Pharmacogenetics of Psoriasis Treatment

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