Parameter | Unit | Estimate | CV % |
L/h | 50 | 0 (fixed) | |
L | 1.5 | 0 (fixed) | |
- | 0.5 | 0 (fixed) | |
1/h | 9.28 | 7.63 | |
L | 61.3 | 24.3 | |
314 | 23.2 | ||
4.95 | 27.7 | ||
L/h | 19400 | 19.5 | |
L/h | 3.86 | 11.5 | |
L | 3 | 0 (fixed) |
Clopidogrel is an anti-platelet compound that is widely used with aspirin to reduce the risk of cardiovascular incidents.In itself it is inactive; only after a biotransformation into its active metabolite clop-AM, does it inhibit platelet aggregation.Recently a system-pharmacological model has been proposed for the network of processes leading to reduced platelet aggregation.In this paper we present a mathematical analysis of this model and demonstrate how the complex pharmacokinetic modelcan be reduced to two simple coupled models, one for clopidogrel and one for clop-AM, yielding insight into the dynamicsof clop-AM and the impact of inter-individual differences on the level of inhibition.
Citation: |
Figure 1.
Schematic model of clopidogrel action on platelet aggregation: clopidogrel travels from the gut to the liver, where one fraction (
Figure 2.
Graph of the clop-AM concentration in plasma (
Figure 4.
Temporal behaviour of
Figure 3.
Graph of the response
Figure 5.
The relative maximal platelet aggregation
Figure 6.
Orbit in the
Table 1. PK parameter estimates
Parameter | Unit | Estimate | CV % |
L/h | 50 | 0 (fixed) | |
L | 1.5 | 0 (fixed) | |
- | 0.5 | 0 (fixed) | |
1/h | 9.28 | 7.63 | |
L | 61.3 | 24.3 | |
314 | 23.2 | ||
4.95 | 27.7 | ||
L/h | 19400 | 19.5 | |
L/h | 3.86 | 11.5 | |
L | 3 | 0 (fixed) |
Table 2. PD parameter estimates
Parameter | Unit | Estimate | CV % |
1/h | 0.00783 | 5.54 | |
1/h | 0.00783 | 5.54 | |
1/ |
4.06 | 4.14 |
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