Role of PKPD Modeling and Simulation in Influencing ... - Pharsight
Role of PKPD Modeling and Simulation in Influencing ... - Pharsight
Role of PKPD Modeling and Simulation in Influencing ... - Pharsight
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Cp (ng/mL)<br />
Case Study 1: Transition<strong>in</strong>g from Precl<strong>in</strong>ical to FIH<br />
Allometric scal<strong>in</strong>g was used to predict human pharmacok<strong>in</strong>etics <strong>of</strong> CS-3030,<br />
an oral, direct Factor Xa <strong>in</strong>hibitor. A comb<strong>in</strong>ation <strong>of</strong> daily doses (10 to 320mg),<br />
regimens (QD <strong>and</strong> BID), <strong>and</strong> bioavailability ranges (4.5 to 50%) was chosen to<br />
compensate for any misspecification due to projection method or underly<strong>in</strong>g<br />
assumptions.<br />
F=0.045 F=0.09 F=0.18 F=0.5<br />
0 4 8 12 20<br />
40<br />
80<br />
160<br />
Parameter Monkey Projected Human<br />
4000<br />
Ka 0.75 h -1 0.75 h -1<br />
2000<br />
V/F 7.6 L 151 L<br />
5 10<br />
20<br />
0<br />
CL/F 0.5 L/h/kg 18.2 L/h<br />
4000<br />
2000<br />
Assumes F = 0.09<br />
0<br />
0 4 8 12 20<br />
0 4 8 12 20<br />
Time (Hr)<br />
S Rohatagi et al., Model based development <strong>of</strong> a direct Factor Xa <strong>in</strong>hibitor, ACoP Meet<strong>in</strong>g, Tucson AZ, Mar 2008<br />
Slide 20<br />
© Tripos, L.P. 2011 All Rights Reserved
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