Alteplase: A Tissue Plasminogen Activator for Acute Myocardial Infarction

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Abstract
Alteplase is a human tissue plasminogen activator (t-PA) produced by recombinant DNA technology. It is a relatively fibrin-specific thrombolytic agent, used primarily to lyse coronary artery clots. It has proven effective in the treatment of acute myocardial infarction (AMI). Despite continuous reevaluation of pharmacokinetic parameters for t-PA, limited distribution and clearance data mandate administration of t-PA as a continuous infusion. Tissue plasminogen activator is eliminated primarily by hepatic metabolism with an elimination half-life of five to ten minutes. Plasma levels show great interindividual variation but correlate with infusion rate and decrease in fibrinogen level. The current recommended dose is 100 mg administered as a 10-mg iv bolus followed by a continuous infusion over three hours. However, 40-150 mg has been used in clinical trials. The compound has undergone extensive testing, comparing it with placebo and streptokinase (SK), and combining it with angioplasty and coronary artery bypass surgery. Tissue plasminogen activator is effective at opening clotted coronary arteries in approximately 70 percent of AMI patients and has been shown to be approximately twice as effective as SK in one U.S. trial. Although there is considerable evidence of efficacy with t-PA, data evaluating the influence of t-PA on mortality are limited, but suggest a reduction to five percent. Currently, thrombolytic therapy is indicated for patients experiencing a transmural AMI with onset of symptoms within three to six hours before presenting to the emergency room. Active internal bleeding or conditions predisposing to serious hemorrhage are contraindications to thrombolytic therapy. In general, there are few side effects with t-PA, the most common being bleeding localized to the catheterization site. Alteplase is approved for administration in AMI. From data generated thus far, we feel this new drug will be a valuable addition to the hospital formulary and will replace streptokinase as the intravenous thrombolytic agent of choice for treatment of AMI.