Pharmacokinetics/Pharmacodynamics of Argatroban Injection in End-Stage Renal Disease Patients Undergoing Hemodialysis

Basic Inclusion Criteria:

• Patients, adult men or women who are between 21 and 75 years of age who are on maintenance hemodialysis regimen for at least three (3) months prior to the study start.
• Patients who can tolerate a hemodialysis session lasting up to 9 hours.
• Patients who can tolerate a hemodialysis treatment with blood flow rates of 300 ml per minute.
• Female volunteers who are not documented to be surgically sterile must be willing to abstain from sexual intercourse during the study or be willing to use intrauterine devices or 2 forms of barrier contraception for at least 7 days prior to the initial dose of study medication and continuing through the completion of the study.

Basic Exclusion Criteria:

• Any clinically relevant abnormality identified per the investigator on the screening medical assessment or laboratory examination.
• History of regular alcohol abuse.
• Treatment with an investigational drug within 30 days.
• History of drug allergy of clinical significance in the opinion of the investigator.
• Currently taking warfarin or other anticoagulants.
• Currently taking NSAIDs (with the exception of aspirin).
• Individuals who are obese.
• Any history of bleeding disorder.
• Any subject with a screening resting systolic blood pressure >180 mmHg and/or resting diastolic blood pressure of >100 mmHg unless, in the opinion of the principal investigator, the blood pressures would not endanger the subject while participating in this trial.
• Concurrent uncontrolled cardiovascular, hematologic, respiratory, CNS, gastrointestinal disease or chronic alcoholism.
• Anemia defined as a hematocrit of < 30 and hemoglobin < 10g/dL.
• Concurrently taking (within the past 30 days) phenytoin, cimetidine, rifampin, cyclosporin or tacrolimus.
• Known hypersensitivity to Argatroban or related compounds.
• Significant hepatic insufficiency as defined by total bilirubin greater than 1.5 mg/dL or transaminase (ALT, AST) elevations greater than 2 times the upper limit of the laboratory reference range.