Table 3.
Parameter estimates and standard errors for the final population pharmacokinetic model for omarigliptin
| Parameter | Final parameter estimate | Interindividual variability | ||
|---|---|---|---|---|
| Typical value | %SEM | Magnitude | %SEM | |
| D1: Zero‐order duration (h) | 0.88 | 5.1 | 75 %CV | 13 |
| FD1: Proportional shift in D1 when FED = 1 | 4.0 | 4.8 | ||
| F0D1: Fixed duration (~0 h) when FORM = 0 (OSF) | −1.0 | FIXED | ||
| F1D1: Proportional shift in D1 when FORM = 1 or 2 (DFC/tablet) | −0.41 | 5.9 | ||
| CL/F: Log apparent unbound renal clearance (L/h) | 1.1 | 1.2 | 27 %CV | 3.9 |
| eGFR: Power coefficient for eGFR on clearance | 0.44 | 3.3 | ||
| V2/F: Log apparent central volume of distribution (L) | 4.5 | 0.13 | NE | NA |
| Effect of patient status on V2 | −0.085 | 15 | ||
| V3/F: Log apparent peripheral volume of distribution (L) | 3.6 | 0.85 | ||
| Q/F: Log apparent intercompartmental clearance (L/h) | 3.3 | 1.7 | ||
| RTC: Log central enzyme concentration (nM) | 1.9 | 2.4 | 42 %CV | 9.4 |
| RTP: Log peripheral enzyme concentration (nM) | 4.0 | 1.7 | 30 %CV | 26 |
| KON: Log association rate constant (1/h × nM) | 0.61 | 54 | NE | NA |
| KEQ: Log equilibrium constant (nM) | 0.92 | 7.5 | ||
| KA: Absorption rate constant (1/h) | 1.9 | 5.7 | 71 %CV | 11 |
| Residual error for phase 1 dataa | 0.055 | 1.0 | NA | NA |
| Residual error for phase 2/3 dataa | 0.10 | 1.8 | NA | NA |
%CV = coefficient of variation expressed as a percentage; %SEM = standard error of the mean expressed as a percentage; DFC = dry‐filled capsule formulation; eGFR = estimated glomerular filtration rate; NA = not available; NE = not estimated; OSF = on‐site formulation
a
Residual variability (%CV) for Phase 1 data was √0.055 × 100 = 23% and for Phase 2/3 data was √0.10 × 100 = 32%.