Acylated plasminogen-streptokinase activator complex: a new approach to thrombolytic therapy.

Acylated plasminogen-streptokinase activator complex (APSAC; antistreplase) is an inactive complex of human plasminogen and streptokinase. When it is injected, a controlled deacylation of the catalytic center occurs, activating the complex so that thrombolysis may begin. This process extends the half-life of streptokinase, allowing for 4-6 hours of fibrinolytic activity. Anistreplase has demonstrated equivalent efficacy to intracoronary streptokinase with regard to reperfusion rates in acute myocardial infarction. In addition, patients have shown a 56% reduction in mortality at 28 days with anistreplase compared to heparin. The adverse effect profile of anistreplase includes minor bleeding and hematoma formation at the site of venipuncture, hypotensive and bradycardic episodes, arrhythmias, facial flushing, fever, and rarely, allergic reactions. Serious bleeding reactions are uncommon, with the frequency of cerebrovascular accident reported at 0.4-0.6%. The special advantage of anistreplase is its administration as a 30-U intravenous bolus injected over 5 minutes, eliminating the need for long infusions and increasing the ease of administration. Based on its efficacy and ease of administration, anistreplase may become the drug of choice in the emergency treatment of acute myocardial infarction.

Epoetin: human recombinant erythropoietin.

The chemistry, pharmacology, pharmacokinetics, clinical uses and efficacy, adverse effects, drug interactions, dosage and administration, and formulary considerations of epoetin are described. Erythropoietin, a glycoprotein hormone primarily synthesized in the kidney, is the chief regulator of red blood cell production. Erythropoietin concentrations increase in response to a hypoxic state, resulting in increased red blood cell formation, accelerated hemoglobin production, and premature movement of reticulocytes into the circulation. The human gene responsible for the production of erythropoietin recently was cloned, and the recombinant product--epoetin--has been made available through mass production. The apparent volume of distribution of i.v. epoetin approximates the assumed plasma volume both in healthy volunteers and in patients with chronic renal failure. Little is known about the metabolism and route of elimination of epoetin and erythropoietin. Epoetin recently was approved by the FDA for treatment of anemia associated with chronic renal failure. Clinical trials in patients receiving hemodialysis or peritoneal dialysis and in predialysis patients with renal dysfunction demonstrate epoetin's efficacy. Other potential indications include augmentation of blood production in patients enrolled in autologous blood donation programs and treatment of anemias associated with rheumatoid arthritis, sickle cell disease, acquired immunodeficiency syndrome, cancer, and premature birth. The most frequent adverse effect associated with epoetin therapy is the worsening or development of hypertension. Other adverse effects include thrombocytosis, hyperkalemia, rise in serum urea concentration, iron deficiency, and flu-like symptoms. No drug interactions with epoetin have been reported in humans. The recommended starting epoetin dosage in patients with chronic renal failure is 50-100 IU/kg three times weekly. Epoetin is available only as an injection for i.v. or s.c. administration. Epoetin provides a new therapeutic approach to the treatment of anemia associated with chronic renal failure in hemodialysis, peritoneal dialysis, and predialysis patients. Benefits of epoetin therapy include reduced need for blood transfusions, the amelioration of anemic symptoms, and an improved quality of life.