hirudin has been researched along with Body-Weight* in 9 studies
1 review(s) available for hirudin and Body-Weight
1 trial(s) available for hirudin and Body-Weight
8 other study(ies) available for hirudin and Body-Weight
| Article | Year |
|---|---|
Toxicology Assessment of a Dual-Function Peptide 5rolGLP-HV in Mice.
5rolGLP-HV had an ideal therapeutic potential in the prevention of hyperglycemia in type 2 diabetes and delay of the thrombosis. The objective of the study was to investigate the toxicology effects of 5rolGLP-HV and guarantee its safety. In acute toxicity test, the mice were orally receiving 5rolGLP-HV at a single dose of 300 mg/kg or 2000 mg/kg. For sub-chronic toxicity study, the mice received 5rolGLP-HV at doses of 800 mg/kg or 1600 mg/kg for 9 weeks. No significant adverse effects were evident in acute and sub-chronic toxicity tests, indicating that the LD50 value is greater than 2000 mg/kg. Although the liver and kidney exhibited a little abnormal in sub-chronic toxicity study, they could recovery to normal after withdrawal 5rolGLP-HV for 2 weeks. In micronucleus assay, the mice received 5rolGLP-HV at doses of 250, 500, or 1000 mg/kg for two consecutive days. The micronucleus numbers and the polychromatic erythrocytes to normochromatic erythrocytes (PCE/NCE) ratios among 5rolGLP-HV groups were within the normal range. Similarly, sperm aberration test demonstrated that 5rolGLP-HV had no teratogenic effect on the mice sperm. In conclusion, the combined results clearly demonstrated the safety of 5rolGLP-HV and support its use as a drug to treat diabetes and thrombosis. Topics: Administration, Oral; Animals; Body Weight; Dose-Response Relationship, Drug; Female; Glucagon-Like Peptide 1; Hirudins; Kidney; Liver; Male; Mice; Micronucleus Tests; Peptides; Recombinant Fusion Proteins; Spermatozoa; Toxicity Tests; Toxicity Tests, Acute; Toxicity Tests, Chronic | 2016 |
Effectiveness of a pilot intervention to reduce abciximab-related bleeding in patients with acute coronary syndromes.
Reducing bleeding events is a priority in patients diagnosed with acute coronary syndromes (ACS). The effectiveness of optimization measures for reducing abciximab-related bleeding was evaluated through the implementation of a pilot program developed by the Pharmacy and the Cardiology Departments at a tertiary-care hospital.. Percentage of bleeding events.. Intervention was effective in reducing the incidence of the three factors associated with an increased risk of bleeding between the pre-intervention phase (n = 86) and the post-intervention phase (n = 73): unknown body weight (24.4 vs. 1.4 %, p = 0.0001), overdosing (31.4 vs. 0 %, p < 0.0001) and combination with bivalirudin (12.8 vs. 1.4 %, p = 0.016). Bleeding events associated with these factors were numerically reduced in all three cases but these differences were not statistically significant between both periods.. The implementation of a multidisciplinary prevention program can reduce situations associated with an increased risk of bleeding in patients treated with abciximab. Larger scale trials are needed to confirm whether such programs can also reduce the incidence of bleeding at a statistically significant level. Topics: Abciximab; Acute Coronary Syndrome; Aged; Antibodies, Monoclonal; Antithrombins; Body Weight; Cohort Studies; Drug Dosage Calculations; Drug Therapy, Combination; Female; Hemorrhage; Hirudins; Humans; Immunoglobulin Fab Fragments; Incidence; Male; Middle Aged; Peptide Fragments; Pharmacy Service, Hospital; Pilot Projects; Platelet Aggregation Inhibitors; Recombinant Proteins; Retrospective Studies; Risk Factors; Spain; Tertiary Care Centers; Workforce | 2014 |
Comparison of bivalirudin dosing strategies using total, adjusted, and ideal body weights in obese patients with heparin-induced thrombocytopenia.
To compare dosing strategies using total body weight (actual measured body weight), adjusted body weight, and ideal body weight when starting bivalirudin for the treatment for heparin-induced thrombocytopenia (HIT) in obese patients, and to compare differences in dosing requirements and clinical outcomes between obese and nonobese patients.. Retrospective medical record review.. Academic tertiary care medical center.. One hundred thirty-five medical and surgical patients who were treated with bivalirudin for HIT between June 1, 2004, and October 1, 2009.. The 135 patients were separated into two groups based on body mass index (BMI): 46 patients had a BMI greater than 30 kg/m(2) and were classified in the obese group; the nonobese group consisted of 89 patients with a BMI less than 30 kg/m(2) . The mean BMI in the obese group was 37.7 kg/m(2) (range: 30.1-56.2 kg/m(2) ). Weight-standardized doses that achieved activated partial thromboplastin time (aPTT) goal were compared in the obese group. The mean ± SD doses that achieved aPTT goal with total (actual), adjusted, and ideal body weights in this group were 0.1 ± 0.07, 0.11 ± 0.08, and 0.14 ± 0.09 mg/kg/hour, respectively. Of the three weight-based dosing approaches, total body weight followed by adjusted body weight provided the closest correlation to rates observed at the target aPTT goal. The secondary analysis compared initial doses of bivalirudin, doses required to reach goal aPTT, time to achieve goal aPTT, and clinical outcomes (number of patients not achieving goal, new thrombosis, major bleeding, and 30-day all-cause mortality) between the obese and nonobese groups. A significant difference in initial dose was noted between groups; however, no significant differences in dose required to achieve goal aPTT, time to achieve goal aPTT, and clinical outcomes were noted between the obese and nonobese groups.. This study provides evidence that the dosing strategy for bivalirudin based on total body weight is the most accurate predictor of achieving aPTT goal in obese patients with HIT. The study also suggests that there are no clinical differences that warrant different dosing strategies between obese and nonobese patients. Further prospective studies are needed to confirm these findings. Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Body Weight; Dose-Response Relationship, Drug; Female; Heparin; Hirudins; Humans; Ideal Body Weight; Male; Middle Aged; Obesity; Partial Thromboplastin Time; Peptide Fragments; Recombinant Proteins; Retrospective Studies; Thrombocytopenia; Young Adult | 2012 |
Intracerebral hirudin injection attenuates ischemic damage and neurologic deficits without altering local cerebral blood flow.
There has been considerable interest in the use of thrombin inhibitors to reduce the occurrence of stroke or to potentiate tissue plasminogen activator-induced reperfusion. However, there is growing evidence that thrombin may also have extravascular effects that influence ischemic brain injury. Male Sprague-Dawley rats were subjected to either 90 minutes of temporary middle cerebral artery (MCA) occlusion or sham operation to examine thrombin and protease activated receptor-1 (PAR-1) expression. In another set of rats, the MCA was occluded for 90 minutes and 10 U of hirudin or the same volume of vehicle was injected into the caudate followed by reperfusion for up to 28 days, to test the effects of local thrombin inhibition on ischemic damage, neurologic outcome and cerebral blood flow (CBF). Thrombin immunoreactivity was increased in the ischemic caudate at 4 and 24 hours, whereas PAR-1 expression was unchanged. Hirudin reduced infarct volume in the caudate at 24 hours (79 +/- 41 vs. 115 +/- 20 mm3, P < 0.05) and resulted in a larger residual tissue volume in the caudate at 28 days (17.6 +/- 3.9 vs. 11.8 +/- 6.3 mm3, P < 0.05). Hirudin treatment also had a beneficial effect on body weight and ameliorated neurologic deficits tested by forelimb placing and forelimb use asymmetry during 28 days survival. These beneficial effects of hirudin were not associated with improved regional CBF during reperfusion. These results suggest that, in addition to their effects on coagulation and circulation, thrombin inhibitors also have direct neuroprotective properties and may be considered in stroke therapy. Topics: Animals; Body Weight; Brain; Brain Ischemia; Cerebrovascular Circulation; Fibrinolytic Agents; Hirudins; Infarction, Middle Cerebral Artery; Male; Microinjections; Motor Activity; Neuroprotective Agents; Rats; Rats, Sprague-Dawley; Receptor, PAR-1; Regional Blood Flow; Thrombin | 2004 |
Heparin versus hirudin for acute coronary syndromes.
Topics: Anticoagulants; Antithrombins; Body Weight; Heparin; Hirudins; Humans; Myocardial Infarction | 1997 |
Biologic effects of recombinant hirudin (CGP 39393) in human volunteers. European Hirudin in Thrombosis Group.
The purpose of this study was to investigate the biologic efficacy and pharmacokinetics of different doses of recombinant hirudin administered in single or repeated subcutaneous injections in healthy volunteers.. Hirudin is a highly specific inhibitor of thrombin, the pivotal enzyme in thrombosis. Differences between hirudin and heparin in experimental animals indicate that hirudin may be a superior antithrombotic drug in humans.. The biologic effect of recombinant desulfato-hirudin (CGP 39393) administered as single or repeated (every 8 h for 3 days or every 12 h for 6 days) subcutaneous injections was studied in 231 healthy human volunteers.. Single subcutaneous doses of 0.1, 0.2, 0.3, 0.4, 0.5 and 0.75 mg/kg body weight in 195, 8, 12, 8, 4 and 4 volunteers, respectively, prolonged the activated partial thromboplastin time in a dose-proportional fashion within the 1st 30 min, with a near-maximal effect for 3 to 4 h after the dose. The mean activated partial thromboplastin time increased to 1.48 and 1.93 times baseline values 30 min after single subcutaneous injections of 0.2 and 0.4 mg/kg of CGP 39393, respectively. There was a linear relation over a wide range between the activated partial thromboplastin time prolongation and plasma concentrations of CGP 39393. Plasma clearance was between 1.5 and 1.7 ml/min per kg. The subcutaneous administration of 0.3 and 0.5 mg recombinant hirudin three times a day for 3 days or two times a day for 6 days prolonged the activated partial thromboplastin time by 1.71 to 1.69 and 1.78 to 1.92 times baseline levels, respectively, with the preinjection values maintained in the hypocoagulable range. No prolongation of bleeding time was measured at peak plasma hirudin levels. Because thrombin and prothrombin times are not able to reflect high or low CGP 39393 concentrations, respectively, neither test is suitable for monitoring administration of this drug.. CGP 39393 appears to be well tolerated in volunteers, even after repeated doses. The activated partial thromboplastin time test seems to be well suited to monitor the anticoagulant effect of recombinant hirudin because the dose effect is linear up to 0.5 mg/kg of subcutaneous CGP 39393. The prolongation of activated partial thromboplastin time after subcutaneous injection of CGP 39393 shows a plateau lasting for 3 h. Further studies are now required to determine the dose that will provide the best antithrombotic effect and the lowest bleeding tendency in arterial or venous thrombosis indications. Topics: Biological Availability; Bleeding Time; Body Weight; Dose-Response Relationship, Drug; Drug Evaluation; Drug Monitoring; Fibrinolytic Agents; Hirudin Therapy; Hirudins; Humans; Injections, Subcutaneous; Linear Models; Metabolic Clearance Rate; Molecular Weight; Partial Thromboplastin Time; Prothrombin Time; Recombinant Proteins; Sensitivity and Specificity; Thrombin Time | 1993 |
Toxicological studies with recombinant hirudin.
After daily administration of 1 mg/kg over a period of 4 weeks, hirudin did not influence growth and general behaviour of the animals. There was no indication of treatment-related effects on the liver and the kidneys, on number and function of thrombocytes, on number and differentiation of white cells or on the erythrocytic system. Haemorrhagic complications did not occur. Formation of antibodies was not detectable. Histopathological changes due to application of r-hirudin were not found. LD50 is greater than 50 mg/kg body weight for intravenous application. Topics: Animals; Behavior, Animal; Biopsy; Body Weight; Drug Administration Schedule; Female; Hematologic Tests; Hirudins; Male; Mice; Mice, Inbred ICR; Rats; Rats, Inbred Strains; Recombinant Proteins; Urine | 1988 |
Pharmacological survey of recombinant hirudin.
The pharmacological properties of a genetically engineered recombinant hirudin (r-hirudin) were studied in animal experiments. r-Hirudin proved to be a well tolerated substance. I.v. injection of up to 200 mg/kg did not lead to perceptible functional or morphological changes. There were no treatment-related effects on the cardiovascular system of dogs and rats after administration of up to 10 mg/kg. After long-term treatment (4 weeks, 1.0 mg/kg daily), no r-hirudin-related histopathological, haematological or biochemical changes could be found. Formation of antibodies was not detectable. Absorption, distribution, and elimination of r-hirudin were studied in dogs and rats. Pharmacokinetics could be best described by an open two-compartment model with first-order kinetics. After i.v. injection in dogs, r-hirudin is distributed into the extracellular space and eliminated through the kidneys in active form by glomerular filtration. After i.v. administration, a half-life of about 1 h was estimated; s.c. administration prolonged the apparent half-life. Pulmonary absorption was shown. Enteral absorption, placental transfer as well as transfer through the fetal integument were very low. r-Hirudin did not pass the blood-brain barrier. The efficacy of r-hirudin in preventing both venous and arterial thrombosis, vascular shunt occlusion or disseminated intravascular coagulation was demonstrated in rats. Depending on the dose, r-hirudin was able to prevent or reduce stasis-induced venous thrombosis, prolong the patency of an extracorporeal arteriovenous shunt, reduce the incidence of arterial thrombosis caused by vascular wall lesions as well as of microthrombosis induced by thrombin infusion.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: Animals; Behavior; Body Weight; Dogs; Female; Fibrinolytic Agents; Hemodynamics; Hemorrhage; Hirudins; Iodine Radioisotopes; Male; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Nephrectomy; Pregnancy; Rabbits; Rats; Rats, Inbred Strains; Recombinant Proteins; Respiration | 1988 |