• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.369-376
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• 2007

Cyclosporine (CsA) and tacrolimus (FK506) have a narrow therapeutic range, and their pharmacokinetic (PK) characteristic varies among individual. They are also substrates for cytochrome P450 (CYP) 3A4, 3A5 genes, and P-glycoprotein, the product of the multidrug resistance 1 (MDR1). The aims were to investigate the relationship between CYP3A and MDR1 genotypes and their PK parameters among healthy subjects. We investigated the genotype for CYP3A and MDR1 gene in human using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. After oral administration of CsA and FK506 (100 mg and 1 mg, respectively), whole blood samples were taken up to 24 hours. Blood CsA and FK506 concentrations were measured by LC/MS/MS. Each PK parameters were compared using Kruskal-Wallis test according to the CYP3A and MDR1 genotype. We found that the values of AVC for CsA were significantly different among CYP3A5 and MDR1 exon 26 (C3435T) genotypes (P=0.037 and P=0.049). On the other hand, the AUC for FK506 was significantly different only among CYP3A5 genotypes (P=0.013). The results clearly demonstrate the effects of CYP3A5 and MDR1 exon 26 on Cys and FK506 disposition.

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.6
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• pp.405-417
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• 2022

Oral lichen planus (OLP) is a chronic inflammatory immune-mediated condition that has been identified as a potentially malignant oral disorder. Various therapies have been proposed for its management as alternative to corticosteroids. However, no definitive treatment has been identified that can result in complete remission or minimal recurrence. Hyaluronic acid has recently been used as an alternative therapy for the management of OLP. This study aimed to systematically review the effectiveness of Hyaluronic acid in the management of symptomatic OLP. Online electronic databases and manual searches were performed for randomized controlled trials (RCTs) published in English between January 2010 and April 2022. RCTs were identified that compared the efficacy of hyaluronic acid and other interventional therapies at baseline and during follow-up. The Cochrane Risk of Bias tool was used to assess the quality of the included studies. Visual analog scale (VAS) scores, Thongprasom sign scores, lesion size, degree of erythema, clinical severity, and disease severity were assessed both quantitatively and qualitatively. Seven studies were analyzed. Five studies reported a high risk of bias while the remaining two studies reported an unclear risk of bias. The overall quantitative assessment of size, symptoms, degree of erythema, and sign score in OLP lesions treated with HA was not statistically significant compared to that in the control group (P > 0.05). In addition, subgroup analysis comparing HA with placebo or corticosteroids did not yield statistically significant (P > 0.05) results. Qualitatively, both HA and tacrolimus resulted in an effective reduction in signs and symptoms. Clinical/disease severity index/scores were inconsistent. A high degree of heterogeneity was observed among the included studies. None of the included studies reported the side effects of HA. These findings suggest that corticosteroids, tacrolimus, placebo, and HA could be equally effective in OLP management. The clinical/disease severity index or score reduction cannot be determined with certainty. Thus, OLP can be treated with HA as an alternative therapy. Owing to limited clinical trials on HA, high heterogeneity, and high risk of bias in the included studies, definitive conclusions cannot be derived.

• Annals of Hepato-Biliary-Pancreatic Surgery
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• v.28 no.2
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• pp.238-247
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• 2024

Backgrounds/Aims: Prolonged use of steroids after liver transplantation (LT) significantly increases the risk of diabetes or cardiovascular disease, which can adversely affect patient outcomes. Our study evaluated the effectiveness and safety of early steroid withdrawal within the first year following LT. Methods: This study was conducted as an open-label, multicenter, randomized controlled trial. Liver transplant recipients were randomly assigned to one of the following two groups: Group 1, in which steroids were withdrawn two weeks posttransplantation, and Group 2, in which steroids were withdrawn three months posttransplantation. This study included participants aged 20 to 70 years who were scheduled to undergo a single-organ liver transplant from a living or deceased donor at one of the four participating centers. Results: Between November 2012 and August 2020, 115 patients were selected and randomized into two groups, with 60 in Group 1 and 55 in Group 2. The incidence of new-onset diabetes after transplantation (NODAT) was notably higher in Group 1 (32.4%) than in Group 2 (10.0%) in the per-protocol set. Although biopsy-proven acute rejection, graft failure, and mortality did not occur, the median tacrolimus trough level/dose/weight in Group 1 exceeded that in Group 2. No significant differences in safety parameters, such as infection and recurrence of hepatocellular carcinoma, were observed between the two groups. Conclusions: The present study did not find a significant reduction in the incidence of NODAT in the early steroid withdrawal group. Our study suggests that steroid withdrawal three months posttransplantation is a standard and safe immunosuppressive strategy for LT patients.

• Journal of Microbiology and Biotechnology
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• v.30 no.1
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• pp.1-10
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• 2020

FK506, also known as tacrolimus, is a clinically important immunosuppressant drug and has promising therapeutic potentials owing to its antifungal, neuroprotective, and neuroregenerative activities. To generate various FK506 derivatives, the structure of FK506 has been modified by chemical methods or biosynthetic pathway engineering. Herein, we describe the mode of the antifungal action of FK506 and the structure-activity relationship of FK506 derivatives in the context of immunosuppressive and antifungal activities. In addition, we discuss the neurotrophic mechanism of FK506 known to date, along with the neurotrophic FK506 derivatives with significantly reduced immunosuppressive activity. This review suggests the possibility to generate novel FK506 derivatives as antifungal as well as neuroregenerative/neuroprotective agents.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.202.3-203
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• 2003

Calcineurin inhibitors, cyclosporine A (CsA) and tacrolimus (FK506), have been studied extensively regarding their effects on T lymphocytes, but their effects on dendritic cells (DC) are relatively unknown. DC can really capture Ag from dead and dying cells for presentation to MHC class I-restricted CTL. The main targets for the immunosuppressive calcinerin inhibitors, FK506 and CsA. have been considered to be activated T cells, but not antigen presenting cells (APCs). (omitted)

• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2007.05a
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• pp.126-126
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• 2007

• Clinical and Experimental Pediatrics
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• v.54 no.8
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• pp.317-321
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• 2011

Children who suffer from steroid-resistant nephrotic syndrome (SRNS) require aggressive treatment to achieve remission. When intravenous high-dose methylprednisolone fails, calcineurin inhibitors, such as cyclosporine and tacrolimus, are used as the first line of treatment. A significant number of patients with SRNS progress to end-stage renal disease if remission is not achieved. For these children, renal replacement therapy can also be problematic; peritoneal dialysis may be accompanied by significant protein loss through the peritoneal membrane, and kidney allograft transplantation may be complicated by recurrence of SRNS. Plasmapheresis and rituximab were initially used for treatment of recurrent SRNS after transplantation; these are now under consideration as rescue therapies for refractory SRNS. Although the prognosis of SRNS is complicated and unfavorable, intensive treatment in the early stages of the disease may achieve remission in more than half of the patients. Therefore, timely referral of pediatric SRNS patients to pediatric nephrology specialists for histological and genetic diagnosis and treatment is highly recommended.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.21 no.4
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• pp.355-360
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• 2018

Recently, fecal microbiota transplantation (FMT) has been attracting attention as a possible medical treatment of ulcerative colitis (UC). A randomized controlled trial of FMT for children with UC is currently underway. Therapeutic effects of FMT for adults with UC remain controversial. We report two cases of early-onset UC in children. A patient was diagnosed with UC at age 1-year 9-month and underwent FMT at age 2-year 3-month. He attained clinical remission for three weeks after FMT, but then relapsed at four weeks, ultimately undergoing a total colectomy. Another child was diagnosed with UC at 2-year 10-month and she underwent FMT at age 5 years. She has remained in clinical remission following FMT for 24 months and her UC has been maintained without complications with tacrolimus and azathioprine. We report that FMT for early-onset UC appears to be safe and potentially effective.

• 대한임상약리학회:학술대회논문집
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• 2002.12a
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• pp.23-23
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• 2002

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.203.1-203.1
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• 2003

Calcineurin inhibitors, cyclosporine A (CsA)and tacrolimus (FK506), have been studied extensively regarding their effects on T lymphocytes, but their effects on dendritic cells (DC) are relatively unknown. DC can really capture Ag from dead and dying cells for presentation to MHC class I-restricted CTL. The main targets for the immunosuppressive calcinerin inhibitors, FK506 and CsA, have been considered to be activated T cells, but not antigen presenting cells (APCs). (omitted)