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Abbokinase (Urokinase) - Description and Clinical Pharmacology

 
 



DESCRIPTION

Abbokinase® (urokinase) is a thrombolytic agent obtained from human neonatal kidney cells grown in tissue culture. The principle active ingredient of Abbokinase® is the low molecular weight form of urokinase, and consists of an A chain of 2,000 daltons linked by a sulfhydryl bond to a B chain of 30,400 daltons. Abbokinase® is supplied as a sterile lyophilized white powder containing 250,000 IU urokinase per vial, mannitol (25 mg/vial), Albumin (Human) (250 mg/vial), and sodium chloride (50 mg/vial).

Following reconstitution with 5 mL of Sterile Water for Injection, USP, Abbokinase® is a clear, slightly straw-colored solution; each mL contains 50,000 IU of urokinase activity, 0.5% mannitol, 5% Albumin (Human), and 1% sodium chloride (pH range 6.0 to 7.5).

Thin translucent filaments may occasionally occur in reconstituted Abbokinase® vials (see DOSAGE AND ADMINISTRATION).

Abbokinase® is for intravenous infusion only.

Abbokinase® is produced from human neonatal kidney cells (see WARNINGS). No fetal tissue is used in the production of Abbokinase®. Kidney donations are obtained exclusively in the United States from neonates (birth to 28 days) for whom death has not been attributed to infectious causes and that have exhibited no evidence of an infectious disease based in part, on an examination of the maternal and neonatal donor medical records. The maternal and neonatal donor screening process also identifies specific risk factors for known infectious diseases and includes testing of sera for HBV, HCV, HIV-1, HIV-2, HTLV-I, HTLV-II, CMV, and EBV. Donors with sera testing positive or associated with other risk factors are excluded. During the manufacturing process, cells are tested at multiple stages for the presence of viruses using in vitro and in vivo tests that are capable of detecting a wide range of viruses. Cells are also screened for HPV using a DNA detection-based test and for reovirus using a polymerase chain reaction-based test. The manufacturing process used for this product has been validated in laboratory studies to inactivate and/or remove a diverse panel of spiked model enveloped and non-enveloped viruses, and includes purification steps and a heat treatment step (10 hours at 60°C in 2% sodium chloride). A single vial of Abbokinase® contains urokinase produced using cells derived from one or two donors.

CLINICAL PHARMACOLOGY

Urokinase is an enzyme (protein) produced by the kidney, and found in the urine. There are two forms of urokinase which differ in molecular weight but have similar clinical effects. Abbokinase® is the low molecular weight form. Abbokinase® acts on the endogenous fibrinolytic system. It converts plasminogen to the enzyme plasmin. Plasmin degrades fibrin clots as well as fibrinogen and some other plasma proteins.

Information about the pharmacokinetic properties in man is limited. Urokinase administered by intravenous infusion is rapidly cleared by the liver with an elimination half-life for biologic activity of 12.6 + /- 6.2 minutes and a distribution volume of 11.5 L. Small fractions of the administered dose are excreted in bile and urine. Although the pharmacokinetics of exogenously administered urokinase have not been characterized in patients with hepatic impairment, endogenous urokinase-type plasminogen activator plasma levels are elevated 2- to 4-fold in patients with moderate to severe cirrhosis.1 Thus, reduced urokinase clearance in patients with hepatic impairment might be expected.

Intravenous infusion of Abbokinase® in doses recommended for lysis of pulmonary embolism is followed by increased fibrinolytic activity in the circulation. This effect disappears within a few hours after discontinuation, but a decrease in plasma levels of fibrinogen and plasminogen and an increase in the amount of circulating fibrin and fibrinogen degradation products may persist for 12-24 hours. 2 There is a lack of correlation between embolus resolution and changes in coagulation and fibrinolytic assay results.

Treatment with urokinase demonstrated more improvement on pulmonary angiography, lung perfusion scanning, and hemodynamic measurements within 24 hours than did treatment with heparin. Lung perfusion scanning showed no significant treatment-associated difference by day 7.3

Information based on patients treated with fibrinolytics for pulmonary embolus suggests that improvement in angiographic and lung perfusion scans is lessened when treatment is instituted more than several days (e.g., 4 to 6 days) after onset. 4

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