| Autor: |
Wachsman, M., Mielke, C. Harold, Hayes, J. A., Baker, D. |
| Zdroj: |
Journal of Clinical Pharmacology; Oct2000, Vol. 40 Issue 10, p1121-1128, 8p |
| Abstrakt: |
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 IV 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. [ABSTRACT FROM PUBLISHER] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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