Predicting pharmacodynamic response to tissue plasminogen activator: a preliminary report.
All thrombolytic agents have produced significant variation in clinical response (patency, reocclusion, bleeding) when administered in recommended doses in patients with myocardial infarction. We have evaluated the in vitro clot lysis response in 19 normal subjects and the pharmacodynamic response to tissue plasminogen activator (TPA) in 9 patients with myocardial infarction using a new, fresh, whole blood clot lysis system. Further, we have developed a Bayesian forecasting system for predicting response to TPA. Sensitivity to TPA (slope of the concentration/log response curve) varied significantly in patients with myocardial infarction (mean, 1.05 +/- 1.1). The mean clearance, volume of distribution, and half life were 55 +/- 13 L/h, 41 +/- 47 L, and 0.41 +/- 0.46 h. Using from zero to three clot lysis feedback times, the mean percentage mean absolute error varied from 65 to 16.4%. A relationship between mean clot lysis time and clinical reperfusion was established. Thus, a system for quantitating and predicting response to TPA was developed and successfully tested. Future extensive clinical trials will be necessary to evaluate fully the use of this system in clinical practice.
Mungall
D
D
Department of Pharmacy, Ferris State University, Lansing, Michigan.
Porter
R S
RS
Reisdorf
E J
EJ
D001499:Bayes Theorem; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000188:drug therapy; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D014914:Whole Blood Coagulation Time
D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator