Table 2.
Final pharmacokinetic and pharmacodynamic model parameter estimates
| Parameter | Estimate | (RSE%) | BSV (%) | (RSE%) |
|---|---|---|---|---|
| CL/F (l h –1 ) | 16.6 | (3.6) | 24 | (8.1) |
| Q/F (l h –1 ) | 10.4 | (4.7) | 95 | (45) |
| Vc/F (l) | 156 | (4.2) | ||
| Vp/F (l) | 55.8 | (8.3) | ||
| KTR (h −1 ) | 10.1 | (5.8) | 54 | (7.9) |
| Absorption lag time prior MI (h) | 0.48 | (11) | ||
| F rel | 1 FIX | 32 | (6.6) | |
| Proportional residual error ticagrelor (%) | 32 | (4.5) | ||
| CL m /F (l h –1 ) | 10.2 | (3.0) | 28 | (9.2) |
| F m | 0.22 FIX | |||
| Q m /F (l h –1 ) | 4.41 | (4.7) | ||
| Vc m /F (l) | 7.04 | (6.7) | ||
| Vp m /F (l) | 42.3 | (6.1) | 37 | (29) |
| Proportional residual error metabolite (%) | 26 | (4.9) | ||
| PRU baseline ONSET/OFFSET |
311 261 |
(1.9) (1.7) |
35 (add*) |
(8.9) |
| PRU baseline PEGASUS | ||||
| EC 50 (nmol l –1 ) | 116 | (5.3) | 66 | (7.1) |
| PRU baseline ‐EC 50 correlation | 0.33 | (27) | ||
| E max (%) | 98.5 | (0.1) |
2.2 (logit*) |
(6.1) |
| Steepness of exposure‐response (γ) | 1.59 | (3.4) | ||
| Additive residual error PRU (at PRU = 300) | 47.6 | (5.6) | ||
| Exponent for PRU error (α) | 0.48 | (2.8) |
CL/F, ticagrelor apparent clearance; Q/F, ticagrelor inter‐compartment clearance; Vc/F, ticagrelor central volume of distribution; Vp/F, ticagrelor peripheral volume of distribution; KTR, absorption transfer rate constant; Frel, ticagrelor relative bioavailability; CLm/F, metabolite; apparent clearance; Fm, fraction of ticagrelor metabolised to AR‐C124910XX; Qm/F, intercompartment clearance for the metabolite; Vcm/F, central volume of distribution for the metabolite; Vpm, peripheral volume of distribution for the metabolite; PRUbaseline, baseline P2Y12 reaction units (PRU); Emax, maximal platelet inhibition; EC50, ticagrelor concentration at half Emax; γ, steepness of the concentration‐response curve; α, Exponent for PRU residual error. PRU residual error was described by a power function, (PRU/300)α × SDat PRU 300; BSV, between subject variability (*standard deviation for PRUbaseline and Emax); RSE%, relative standard error (100*SE/mean); the RSE for BSV are reported on the approximate standard deviation scale (SE/variance estimate)/2; Emax is derived from the estimated parameter logit (Emax) and the RSE is based on numerical integration from the normal distribution of logit (Emax)