Table 2.
Population pharmacokinetic/pharmacodynamic parameter estimates
| Parameters | Estimate (RSE%) | ISV (RSE%) | Bootstrap analysis Median [5
– 95th percentiles] |
|
|---|---|---|---|---|
| Estimate | BSV | |||
| CL/F (L/h) | 84.79 (11.91) | 36.55 (51.16) | 79.48 [64.33 – 98.44] | 36.18 [17.26 – 49.99] |
| VC/F (L) | 176.43 (16.39) | 63.19 (60.85) | 169 [125.89 – 223.47] | 62.02 [28.11 – 99.19] |
| ka (h−1) | 0.22 (7.47) | 0.22 [0.20 – 0.25] | ||
| Q/F (L/h) | 14.29 (13.25) | 13.14 [10.47 – 16.45] | ||
| VC/F (L) | 217.62 (13.19) | 41.53 (44.80) | 207.51 [160.11 – 249.82] | 40.71 [26.14 – 56.78] |
| F | 1 FIXED | 85.70 (38.37) | 84.56 [46.72 – 107.44] | |
| Residual error [log(ng/mL)]a | 0.70 (17.66) | 0.70 [0.51 – 0.93] | ||
|
| ||||
| DPP40 (RLU) | 3573.82 (5.83) | 20.12 (60.71) | 3608 [3239 – 3932] | 19.53 [1.34 – 28.20] |
| ksyn(h−1) | 3924.63 (13.07) | 56.60 (43.95) | 3788 [2963 – 4481] | 54.25 [25.43 – 75.93] |
| kf (h−1) | 0.06 (21.43) | 0.06 [0.05 – 0.09] | ||
| Emax (unitless) | 7.64 (17.43) | 7.32 [5.78 – 9.93] | ||
| EC50 (ng/mL) | 353.88 (21.56) | 102.17 (38.39) | 357.57 [296.57 – 530.99] | 101.33 [54.53 – 129.86] |
| h (unitless) | 1.76 (9.95) | 1.75 [1.48 – 2.05] | ||
| (unitless) | 0.80 (16.98) | 0.79 [0.63 – 1.06] | ||
| Cov(2EC50, 2F) | 86.08 (44.22) | 85.04 [31.65 – 110.50] | ||
| Residual error [log(RLU)]a | 0.20 (11.12) | 0.20 [0.16 – 0.24] | ||
Additive error model in log scale
All parameters were simultaneously estimated and listed here twith their corresponding relative standard error (RSE%); BSV, between subject variability expressed as coefficient of variation (%). CL/F, total apparent oral clearance; VC/F and VP/F, apparent volumes of distribution of the central, and peripheral compartments, respectively; ka, first order rate constant of absorption; Q/F inter-compartmental distribution clearances between the central and peripheral compartment; F, oral bioavailability; DPP40, baseline value for DPP4 activity; ksyn, synthesis rate of DPP4; kf regulates the delay of the feedback loop; Emax, maximum effect; EC50, the drug concentration necessary to achieve 50% of the Emax; h, hill exponent; γ, feedback exponent; 2, variance.