Table 2.
Parameter estimates for plasma pharmacokinetics of the 10 compounds
| Parameter estimates (RSE, %) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Acetaminophen | Atenolol | Methotrexate | Morphine | Paliperidone | Phenytoin | Quinidine | Raclopride | Remoxipride | Risperidone | ||
| CLPL | mL/min | 15.8 (9.10) | 7.13 (20.6) | 8.04 (15.9) | 22.6 (7.70) | 196 (13.0) | 36.0 (8.90) | 162 (4.10) | 46.4 (4.30) | 42.2 (4.90) | 886 (33.2) |
| QPL_PER1 | mL/min | 33.8 (33.7) | NA | 28.5 (30.7) | 30.8 (10.0) | 61.5 (86.2) | 265 (12.7) | 829 (6.80) | 13.4 (27.5) | 33.8 (20.7) | NA |
| QPL_PER2 | mL/min | NA | NA | 3.33 (34.8) | 7.21 (10.2) | NA | NA | NA | 69.2 (7.50) | 14.0 (10.1) | NA |
| VPL | mL | 49.5 (59.0) | 256 (27.0) | 28.0 (55.0) | 152 (11.1) | 26,400 (12.6) | 943 (21.5) | 670 (13.3) | 48.9 (16.3) | 83.7 (18.3) | 43,100 (28.1) |
| VPER1 | mL | 363 (33.1) | NA | 111 (14.6) | 530 (9.10) | 3,580 (35.8) | 2,050 (7.50) | 11,300 (3.20) | 684 (19.2) | 253 (10.9) | NA |
| VPER2 | mL | NA | NA | 83.5 (34.9) | 1,200 (10.8) | NA | NA | NA | 493 (18.3) | 757 (4.00) | NA |
| Fraction | 0.693 (19.6) | NA | NA | NA | NA | NA | NA | NA | NA | NA | |
| Interindividual variabilitya | |||||||||||
| ɷ_CLPL | % | NA | NA | 37.4 (46.8) | 17.8 (39.5) | 42.0 (62.5) | 73.8 (12.5) | 23.9 (15.3) | 14.4 (29.8) | 31.0 (12.0) | 72.5 (38.7) |
| ɷ_QPL_PER1 | % | NA | NA | NA | 28.8 (29.4) | NA | NA | 24.3 (28.2) | NA | 25.1 (12.1) | NA |
| ɷ_QPL_PER2 | % | NA | NA | 42.5 (42.0) | 86.7 (19.3) | NA | NA | NA | NA | 76.7 (13.5) | NA |
| ɷ_VPL | % | NA | NA | 40.4 (75.5) | 80.6 (17.2) | 47.5 (81.4) | 75.0 (27.2) | NA | NA | 64.1 (32.9) | 53.7 (78.8) |
| ɷ_VPER1 | % | 51.8 (86.0) | NA | NA | 46.0 (15.3) | NA | NA | 12.8 (26.6) | NA | NA | NA |
| ɷ_VPER2 | % | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
| Interoccasional variabilityb | |||||||||||
| ɷ_study1 | % | NA | NA | NA | 42.7 (16.2) | NA | NA | NA | NA | NA | NA |
| ɷ_study2 | % | NA | NA | NA | 29.7 (30.5) | NA | NA | NA | NA | NA | NA |
| Residual errorc | |||||||||||
| σ_plasma proportional | % | 23.7 (35.0) | 48.6 (56.1) | 15.1 (17.2) | 24.6 (8.80) | 22.7 (15.6) | 13.0 (10.6) | 24.5 (7.70) | 14.1 (8.60) | 31.0 (11.2) | 47.2 (49.1) |
| σ_plasma additive | ng/mL | NA | NA | 5,400 (42.6) | NA | NA | NA | NA | NA | NA | 0.0244 (27.6) |
CLPL, clearance from the central compartment; Fraction, percentage of the drug which is reabsorbed by enterohepatic circulation; NA, not applicable; QPL_PER1, intercompartmental clearance between the central compartment and the peripheral compartment 1; QPL_PER2, intercompartmental clearance between the central compartment and the peripheral compartment 2; RSE, relative standard error; VPL, distribution volume of the central compartment; VPER1, distribution volume of the peripheral compartment 1; VPER2, distribution volume of the peripheral compartment 2.
a,bθih = θ×e^(ηi+ ηh), where θih represents the parameters of the ith subject and hth study, θ represents the population mean value of the parameter, ηi is the random effect of the ith subject under the assumption of a normal distribution with a mean value of 0 and variance of ω1 2, and ηh is the random effect of the hth study under the assumption of a normal distribution with a mean value of 0 and variance of ω2 2. cCij = YIPRED,ij×(1+ɛij) or Cij = YIPRED,ij×(1+ɛ1,ij)+ɛ2,ij, where Cij represents the jth observed concentration of the ith subject, YIPRED,ij represents the jth individual prediction of the ith subject, and ɛij is the random effect of the jth observed concentration of the ith subject under the assumption of a normal distribution with a mean value of 0 and variance of σ2.