• Korean Journal of Clinical Pharmacy
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• v.20 no.1
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• pp.9-16
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• 2010

Purpose: 본 연구는 한국인 성인 조혈모세포이식환자를 대상으로 경구용 사이클로스포린의 집단약동학 분석을 통하여 사이클로스포린의 약동학적 파라미터에 영향을 미치는 요인 분석을 실시하고자 하였다. Methods: 2000년 12월부터 2006년 8월까지 서울대학교병원에서 동종조혈모세포이식을 받고 면역억제제로 사이클로스포린을 복용한 성인 백혈병환자를 대상으로 후향적으로 자료를 수집하였다. 사이클로스포린의 약동학에 영향을 미치는 인자로는 연령, 성별, 이식 후 날짜, 신기능, 공여자와의 관계, 질병의 종류, 혈중 빌리루빈 농도, 사이클로스포린의 대사를 유도하는 프레드니솔론의 투여량, 헤마토크리트, 사이클로스포린의 대사를 저해하는 약물의 병용여부 등을 검토하였다. 분석은 NONMEM$^{(R)}$ VI 프로그램을 이용하였으며, 변수를 추가하지 않은 기본 모형을 만든 후에 단계적인 요인의 추가와 제거를 통해 최종모형을 제작하였다. Results: 최종 상관 모형은 다음과 같다; CL/F (L/h) = $85.6{\times}e^{(0.646\;{\times}\;HCT/28.9\;+\;0.0464\;{\times}\;Gender)}$. 사이클로스포린의 겉보기 클리어런스는 환자의 성별이 남자일 때 또는 헤마토크릿이 감소할수록 증가하였다. 그 외 파라미터는 다음과 같이 계산되었다; $K_{\alpha}=0.0787\;(h^{-1})$; Q=57.1(L/kg/h); $V_{d-central\;compartment}$=1,100 (L); $V_{d-peripheral\;compartment}$ = 213,000(L). 개체간 편차는 40% 미만이었으며, 개체내 편차를 포함하는 잔차는 24.02%였다. Conclusions: 사이클로스포린의 약동학적 특징과 그 클리어런스에 영향을 끼칠 수 있는 임상적 요인을 이해하는 것은 환자 개개인의 용량과 용법의 결정 및 이상반응 발생의 예방에 유용할 수 있다. 한국인 조혈모세포이식환자에서 사이클로스포린의 약동학에 영향을 미치는 최종 파라미터를 구한 본 연구의 결과는 조혈모세포이식을 받은 한국인 성인환자에서 사이클로스포린의 모니터링 및 용량조절에 유용할 것으로 전망된다.

• Journal of the korean academy of Pediatric Dentistry
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• v.45 no.3
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• pp.271-279
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• 2018

Previous studies to elucidate the etiology of cyclosporine(Cs)-induced gingival overgrowth in children have not completely excluded all factors that may cause differences among individuals. This study examined the effect of cyclosporine on the metabolism of type 1 collagen(CoL-I) in experimental models that controlled the effects of biological variations on individuals. Five 5-week-old male Sprague-Dawley rats were administered Cs by gastric feeding for 6 weeks. Gingival specimens were harvested from the mandibular posterior area before beginning Cs administration and at 2, 4, and 6 weeks thereafter. Gingival fibroblasts were cultured from all the 20 biopsies collected from the gingiva. Half of the fibroblasts collected prior to the Cs administration were designated as Control. The other half of the fibroblasts were treated with Cs in vitro and called in vitro test group(Tt). The fibroblasts collected 2, 4, and 6 weeks after the Cs administration were called in vivo test groups : T2, T4, T6, respectively. Immunofluorescence microscopy was used to detect CoL-I in all the fibroblasts. CoL-I was analyzed at both the gene and protein expression levels by real-time polymerase chain reaction and western blotting. Changes in CoL-I before and after Cs treatment were evaluated from the gingiva of each rat. There was no significant difference in gene expression of CoL-I in the control and test groups. CoL-I protein expression levels of fibroblasts increased in in vitro Cs treatment for each individual, and also increased in in vivo Cs treatment. In this study, the experimental method that control biological variations that can occur due to differences among individuals was useful. Subsequent studies on other factors besides CoL-I and in-depth studies in humans are needed.

• Childhood Kidney Diseases
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• v.6 no.2
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• pp.142-154
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• 2002

Purpose : One of the most important adverse effects of long-term cyclosporine therapy is nephrotoxicity, the morphologic changes of which include interstitial fibrosis and arteriolar hyalinization. Recently, several authors have shown that osteopontin plays an important role in the development of interstitial fibrosis by acting as a macrophage chemoattractant and stimulating the production of $TGF-{\beta}$ in experimental cyclosporine nephrotoxicity. However, the relationship between osteopontin and $TGF-{\beta}$ in humans has not been clearly documented so far. We studied the expression of osteopontin and $TGF-{\beta}$ in children with minimal change nephrotic syndrome treated with cyclosporine to demonstrate whether there is a relationship between cyclosporine toxicity and osteopontin expression as previously shown in animal models. Materials and methods : Nineteen children (15 males and 4 females) were the subject of this study. Renal biopsies had been performed before and after the cyclosporine therapy (mean duration: 15.9 months). In 5 patients, additional biopsies were performed after completing the cyclosporine treatment (mean; 26 months). The expressions of osteopontin and $TGF-{\beta}$ were evaluated by immunohistochemistry in the glomeruli and tubulointerstitium. Results : Osteopontin expression was significantly increased in the glomerular mesangium and tubules after cyclosporine treatment. But there was no statistically significant increase of $TGF-{\beta}$ in the interstitium. There was no significant increase in tubular osteopontin and interstitial $TGF-{\beta}$ expression in those cases developing interstitial fibrosis after cyclosporine treatment compared with cases those not developing interstitial fibrosis. No significant changes in osteopontin or $TGF-{\beta}$ expression were observed in subsequent 5 biopsy samples after discontinuation of cyclosporine compared with the first follow up biopsies. Conclusion : These results suggest that osteopontin is a nonspecific marker of renal injury rather than a mediator of interstitial fibrosis in cyclosporine nephrotoxicity of human.

• Journal of Veterinary Clinics
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• v.26 no.4
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• pp.340-343
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• 2009

A 3-year-old, intact female Poong-san dog was presented with a 4-month history of erosive, erythematous dermatitis unresponsive to systemic antibiotics and glucocorticoids. Crust, erosion, and alopecia were noted on the ear pinnae, bridge of nose, and forelimb. Cytological evaluation of intact pustules showed isolated free-floating rounded acantholytic keratinocytes admixed with non-degenerated neutrophils and eosinophils. Results of histopathologic examination revealed the intra-epidermal pustules with predominant neutrophils, less eosinophils, and isolated and clustered acantholytic cells. A diagnosis of pemphigus foliaceus (PF) was made based on the history, clinical, cytological and histopathological results. The skin lesions had improved after systemic cyclosporine therapy. This case report demonstrates that cyclosporine, an immunosuppressive agent, can be used in the management of PF in dogs.

• Childhood Kidney Diseases
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• v.14 no.1
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• pp.100-104
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• 2010

We report on two children with a high risk of recurrent focal segmental glomerulosclerosis (FSGS) after renal transplantation that could be effectively prevented by prophylactic administration of cyclosporine combined with preemptive plasmapheresis prior to renal transplantation.

• Journal of Veterinary Clinics
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• v.27 no.6
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• pp.751-754
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• 2010

A 6-year-old spayed female Persian cat presented with a 3-month history of recurrent ulcerative keratitis with noticeable opacification and vascularization of the right cornea. The lesion was nonresponsive to topical antibiotics and to nonsteroidal anti-inflammatory drugs. Ophthalmic examination showed signs of ocular discomfort, such as epiphora and blepharospasm, in the right eye. Biomicroscopic examination revealed an irregular, edematous, vascularized mass with pink to white tissue on the entire cornea and mild conjunctivitis. A tentative diagnosis of feline proliferative eosinophilic keratitis (FPEK) was made on the basis of clinical appearance. Cytologic examination of the cornea showed a mixture of numerous eosinophils and mast cells, which confirmed the original diagnosis of FPEK. The cat was treated with a topical antibiotic-corticosteroid combination, cyclosporine ointment, trifluridine eye drops, and oral Llysine. The clinical signs improved remarkably 18 days after the cat was first examined. The short-term use of corticosteroids and long-term use of cyclosporine and an anti-viral agent resolved the lesion without recurrence of the disease for 1 year.

• 대한핵의학회:학술대회논문집
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• 2002.11a
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• pp.20.1-20.1
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• 2002

• Childhood Kidney Diseases
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• v.11 no.1
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• pp.92-99
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• 2007

The posterior reversible encephalopathy syndrome(PRES) is characterized clinically by a combination of acute or subacute confusion, lethargy, visual disturbance, and seizures. PRES has been described in various clinical settings, including severe hypertension, chemotherapy, eclampsia, and seizure. We report a case of a 7-year-old girl who had taken cyclosporine for steroid resistant nephrotic syndrome. Twenty one days after the cyclosporine therapy, she was admitted due to generalized tonic clonic seizure and headache. Her blood pressure was 170/90 mmHg. Magnetic resonance(MR) imaging showed necrotic/cystic lesions involving the bilateral parieto-occipital region. After discontinuation of cyclosporine, and control of blood pressure, she had no more seizure and headache. The follow-up MR examination which was performed 6 months later showed the decreased extent of the lesion.

• Journal of Chest Surgery
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• v.38 no.9 s.254
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• pp.595-600
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• 2005

Background: Colchicine with its immunosupressive properties has been used with benefcial effects in autoimmune disease, such as Gout, etc. Whether colchicine, by virtue of the above property, could attenuate the process of cardiac allograft rejection in the rats is investigated in this report. Material and Method: We compared the untreated group (Control, n=6), Cyclosporin A group (10 mg/kg, daily, n=20), and Colchicine derivative group (Colchicine 40 ${\mu}g$/kg, n=20) of cardiac allografts in the rats. Result: In the untreated control group (n=6), all of 6 rats showed rejection within 3 weeks after cardiac allograft. In the cyclosporin A group (n=20), cyclosporin A (10 mg daily oral dose) was administered at a 10 mg daily oral dose and promoted long-term survival (over 100 days). The cyclosporin A group had one mortality at the 18th post-operative day due to infection. Furthermore, in the Colchicine derivatives group (n=20) with a daily IP (Intra Peritoneum) dose (40 ug/kg/day), we observed long-term survival.(> 100 days), except for one rat that died of an anesthetic problem (respiratory failure) at the 9th post-operative day. Conclusion: Experiments have also been performed to evaluate whether the effect of colchicine derivatives allowed prolonged survival of cardiac allografts compared with the cyclosporin A administration group in the rats.

• YAKHAK HOEJI
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• v.39 no.5
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• pp.487-494
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• 1995

Solid lipid microspheres (SLMs) were prepared using various lipids and solidifying agents, in order to enhance the gastrointestinal absorption of Cyclosporine A (Cs A) which is a practically water-insoluble drug with low systemic bioavailability. Egg lecithin and HCO-60 (polyoxyethylated 60 mol, hydrogenated castor oil) were used as lipids. Stearic acid and stearyl alcohol were used as solidifying agents. Emulsion concentrates containing Cs A were prepared by mixing the melted lipid and solidifying agent with water, employing bile salts as a cosurfactant. SLMs were obtained by dispersing the warm emulsion concentrate in cold distilled water under mechanical stirring, followed by freeze drying. Physical characteristics of each SLM were investigated by particle size analysis, optical microscopy and scanning electron microscopy. Mean particle size of SLMs was in the range of 30 to 40.mu.m. The SLMs were in good appearance with spherical shape before freeze drying, but were deformed partially after freeze drying. Drug loading efficiencies of SLMs were observed as high as 80 to 90% in average. The systemic bioavailability of Cs A from different SLM formula was investigated in rats following oral administration. Cs A in whole blood was extracted and assayed by HPLC. SLMs revealed the higher bioavailabilities than the standard formula based on the marketed product. SLMs might have several advantages over standard formula for enhanced gastrointestinal absorption, controlled release properties, high loading capacity of the water-insoluble drug, and feasibility of solid dosage forms with better stability in storage.