The use of time step simulations and difference equations (TSSADEQ) in modeling heparin pharmacokinetics.
A model in which the clearance of heparin requires the binding of heparin to a finite and regenerated pool of binding was constructed using time step simulations and difference equations (TSSADEQ). A simulation of a heparin i.v. bolus demonstrated a dose-dependent, triphasic pharmacokinetic curve with (1) an initial log-linear phase representing first-order association of heparin with binding sites, (2) an intermediate plateau phase representing constant regeneration of heparin binding sites, and (3) a terminal log-linear phase occurring when the quantity of regenerated sites exceeded the remaining heparin. Sensitivity analysis based on the literature produced estimates of the k at 1.39 to 2.77 h-1, the pool of binding sites of 50 units/kg, and the regeneration rate of 15 to 20 unit/kg/h--virtually identical to the empirically derived guidelines for the bolus size and infusion rate for unfractionated heparin. A pilot study of bolus dosing of unfractionated heparin in normal volunteers confirmed the model.
Wachsman
M
M
Harford Memorial Hospital and Cassandra Associates, Havre de Grace, Maryland 21078, USA.
Mielke
C H
CH
Hayes
J A
JA
Baker
D
D
D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics; D003198:Computer Simulation; D005260:Female; D006493:Heparin / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results; D012984:Software; D013997:Time Factors
D000925:Anticoagulants; D006493:Heparin