• Journal of Pharmaceutical Investigation
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• v.39 no.5
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• pp.373-379
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• 2009

This study was conducted to develop a pharmacokinetic-pharmacodynamic (PK/PD) model of a direct thrombin inhibitor, argatroban to predict the concentration-effect profiles in rats. Argatroban was i.v. injected to rats at 0. 2, 0.8 and 3.2 mg/kg doses (n = 4-5 per dose), and plasma drug levels were determined by a validated LC/MS/MS assay. The pharmacokinetics of argatroban was linear over the i.v. dose range studied. The thrombin time (TT) and the activated partial thromboplastin time (aPTT) were measured in rat plasma and they were found to linearly increase with increasing the dose. A 2-compartment pharmacokinetic model linked with an indirect response pharmacodynamic model was successfully utilized to evaluate the drug concentration-response relationship.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.4
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• pp.300-305
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• 2005

Purpose: For the reconstruction of maxillofacial defect created by trauma, infection, or tumor etc, the role of microvascular anastomosis or vessel graft has been increased. Many methods has been tried to increase the success rate of microvascular anastomosis. Various anticoagulants and thrombolytic agents have been used to reduce the failure rate of microvascular anastomosis and avoid re-operation. Many drugs, however, have been used in the limited cases because most of these drugs may cause complications, such as allergy, fever or systemic bleeding. This study was performed to evaluate the influence of the Argatroban on patency and thrombosis in microvascular anastomosis when it is used for local irrigation or general administration. Materials & methods: Eight mature rabbits, weighing 2kg, were used. After exposing both femoral veins, the artificial thrombotic model was made by crushing injury using a smooth needle holder, and the transverse incision were made on femoral vein. The animals were divided into 4 groups according to Argatroban administration methods; control group (n=4), topical irrigation of lumen with saline solution; experimental group 1 (n=4), topical irrigation of lumen with Argatroban saline solution; experimental group 2 (n=4), topical irrigation of lumen with heparin followed by intravenous injection of Argatroban; experimental group 3 (n=4), topical irrigation of lumen with Argatroban followed by IV of Argatroban. Microvascular anastomosis was done with 10-0 Ethilon. The patency was evaluated by empty-and-refill test 30 minutes and 3 days after microanastomosis. The thrombus formation was examined 3 days after microanastomosis by surgical microscope. The histologic findings were also examined. Results: 1. Thirty minutes after microvascular anastomosis, the patency of all experimental groups was better than that of control group, but there was no significant difference among groups. 2. Three days after microvascular anastomosis, the patency of all experimental groups was more improved than that of control group (p<0.05). There was no significant difference among experimental groups. 3. Three days after microvascular anastomosis, the amount of thrombus in all experimental groups was less than that of control group (p<0.05). There was no significant difference among experimental groups. 4. Histologically, a lot of luminal thrombus was observed around sutured area in control group. Few luminal thrombus was observed in all experimental groups. The necrotic changes were observed on the sutured vein wall in all specimens. Conclusion: These results indicate that topical irrigation and/or intravenous administration of Argatroban is effective in improving patency and preventing thrombus formation after microvascular anastomosis.

• Journal of Korean Neurosurgical Society
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• v.47 no.4
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• pp.258-264
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• 2010

Objective : The objectives of this study were to analyze the outcome and hemorrhagic risk of intravenous (IV) argatroban in patients with acute ischemic stroke presenting beyond six hours of ischemic symptom onset. Methods : Eighty patients with acute ischemic stroke who were admitted to the hospital beyond six hours from ischemic symptom onset were retrospectively analyzed. We could not perform IV thrombolysis or intra-arterial thrombolysis because of limited time window. So, IV argatroban was performed to prevent recurrent thrombosis and progression of infarcted area. The outcome was assessed by the National Institute of Health Stroke Scale (NIHSS) score and related hemorrhagic risk was analyzed. Also, each outcome was analyzed according to the initial stroke severity, subtype, and location. Results : The median NIHSS was 8.0 at admission, 4.1 upon discharge, and 3.3 after three months. A good outcome was achieved in 81% of patients upon discharge and 88% after three months. Symptomatic hemorrhage occurred in only two patients (3%). IV argatroban was effective regardless of initial stroke severity, subtype, and location. Conclusion : IV argatroban may be an effective and safe treatment modality for acute ischemic stroke presenting beyond six hours of ischemic symptom onset.

• Journal of Chest Surgery
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• v.43 no.5
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• pp.538-541
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• 2010

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic condition and adverse drug reaction caused by immunoglobulin G (IgG) antibodies directed against the heparin-platelet factor 4 complex. HIT with thrombosis (HITT) could lead to limb amputation, stroke, myocardial infarction, and death. We report on the successful management of a HITT patient with argatroban therapy.

• The Journal of Internal Korean Medicine
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• v.28 no.4
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• pp.863-871
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• 2007

Objects : To gain better insights of East-west integrated treatment of ischemic stroke. We analyzed 89 patients with severe acute ischemic stroke who were admitted to the East-west integrated intensive care unit. Methods : Subjects enrollment was from the East-west integrated intensive care unit of Kyung Hee Medical Center from March 2006 to February 2007. Patients were admitted within 14 days after the onset of ischemic stroke. We assessed the subjects' general characteristics, risk factors, admitting routes and periods, diagnostic imaging, process of western treatment and Korean traditional treatment, complication and consequence. Results : The proportion of males was 50.6%, of females 49.4%, average age was male 66.0$\pm$10.3 and female 71.1$\pm$10.5. Average length of hospital stays was 19.5 days. Monthly admissions were highest in November and December. The admission route was through emergency room (61.8%) or ward (34.8%). Mean Glasgow coma scale score was 10.0$\pm$2.5, average time from symptom of onset to hospital admission was 2.3$\pm$2.2 days. Dominant ischemic vascular territory was middle cerebral artery (66.3%). Initial western treatment was argatroban (22.5%), urokinase (28.1%), and heparinization (38.2%). Distribution of Sasang constitution of So-yang to Tae-eum to So-eum was equal to 5.4 to 2.9 to 1.5. Major complications were observed in 40 (42.7%) patients. In hospital mortality was 12.4% (11 deaths), all of them caused by aggravation of neurological deficit and only 3 of them with major complications. There appears to be a significant positive relationship between length of hospital stay and occurrence of complications (P<0.05). After discharge from the ICU, 64 (71.9%) patients were improved, 11 (12.4%) patients had expired, and 14 (15.8%) patients were transferred. Conclusions : From this study, we suggest that patients with severe acute ischemic stroke should be treated with East-west integrated therapy for more favorable consequences and decreased mortality.