Table 3.
Final model parameter estimates (model 4).
| Pharmacokinetic parameter | Symbol | Point estimate (IIV CV%) | Bootstrap median (95% CI) |
|---|---|---|---|
| Non-renal clearance (L/h) | CLNR | 0.254 (–) | 0.251 (0.0232 to 0.257) |
| Renal clearance (L/h) | CLR | 8.08 (32.8) | 8.00 (7.17 to 8.91) |
| Apparent central volume of distribution (L) | V2/F | 109 (15.7) | 107 (92.1 to 121) |
| Intercompartmental clearance (L/h) | Q/F | 61.1 (10.3) | 60.1 (54.1 to 67.8) |
| Apparent peripheral volume of distribution (L) | V3/F | 774 (17.9) | 765 (682 to 879) |
| Zero-order absorption duration (h) | D2 | 0.536 (27.8) | 0.521 (0.464 to 0.577) |
| Lag time for zero order absorption (h) | ALAG2 | 0.0955 (48.0) | 0.0940 (0.0781 to 0.105) |
| First order absorption rate constant (1/h) | Ka | 0.636 (68.5) | 0.658 (0.500 to 1.04) |
| Lag time for first order absorption (h) | ALAG1 | 2.43 (11.8) | 2.42 (2.20 to 2.71) |
| Percentage of first order absorption | FF1 | 0.267 (18.4) | 0.278 (0.217 to 0.343) |
| Relative difference in bioavailability in trial I compared to trial II | BIO | − 0.303 (13.1) | − 0.304 (− 0.392 to − 0.218) |
| Relative difference in bioavailability for CGC/CGT compared to the CGC/CGC ABCB1 SNP combination group | BIOH2 | 0.350 (–) | 0.339 (0.131 to 0.672) |
| Relative difference in bioavailability for CGC/TTT compared to the CGC/CGC ABCB1 SNP combination group | BIOH3 | 0.0613 (–) | 0.0421 (− 0.0757 to 0.203) |
| Relative difference in bioavailability for TTT/TTT compared to the CGC/CGC ABCB1 SNP combination group | BIOH4 | 0.348 (–) | 0.320 (0.167 to 0.490) |
| First order absorption rate constant of test period in trial II (1/h) | KAT | 0.201 (–) | 0.197 (0.155 to 0.263) |
IIV CV%, coefficient of variation on inter-individual variability; 95%CI, 95% confidence interval.