Table 1.
Parameter estimates in models for PTV, RIF, and CPI in the healthy population and the population with CKD
| Drugs | Parameters (units) | Estimate (RSE) | ||
|---|---|---|---|---|
| Populationa | BPVb | |||
| PTV | System parameters | ka PTV (/h) | 0.727 (7) | 10.9 (73) |
| V 1_frac | 0.985 (1) | — | ||
| f d1 | 0.0564 (7) | 29.6 (26) | ||
| CL active,PTV,HV (L/h) | 8,136 (15) | 32.3 (20) | ||
| CL passive,PTV (L/h) | 134 FIXED | — | ||
| CL B,PTV (L/h) | 240 (34) | 47.9 (28) | ||
| Kp PTV | 3.46 (6) | 21.0 (28) | ||
| Covariates | COV CLactive,G2 | 0.29 (3) | — | |
| COV CLactive,G34 | 0.39 (7) | — | ||
| Residual unexplained variabilities | σ prop – PTV (%) | 27.1 (5) | — | |
| σ add – PTV (nM) | 0.00005 FIXED | — | ||
| RIF | System parameters | Tlag RIF (h) | 0.401 (17) | 76.4 (18) |
| Tk0 RIF,male (h) | 0.716 (12) | 34.9 (22) | ||
| V RIF (L) | 38.3 (6) | 26.5 (16) | ||
| CL RIF (L/h) | 6.35 (6) | 26.2 (15) | ||
| K i,total (μM) | 0.345 (6) | — | ||
| Covariates | COV Tk0,SEX | 0.639 (37) | — | |
| COV Vrif,BW | 1.01 (28) | — | ||
| COV CLrif,BW | 0.933 (29) | — | ||
| Corr V RIF and CL RIF | 0.668 (19) | — | ||
| Residual unexplained variabilities | σ prop – RIF (%) | 16.1 (8) | — | |
| σ add – RIF (μM) | 0.2 FIXED | — | ||
| CPI | System parameters | k syn,HV&mild (nmol/h) | 10.6 (11) | 13.4 (26) |
| CL B,CPI (L/h) | 7.23 (13) | — | ||
| CL R,CPI,HV (L/h) | 4.58 (12) | 33.4 (17) | ||
| V C,CPI (L) | 11 (17) | — | ||
| CL active,CPI (L/h) | 1,040 (22) | 28.9 (19) | ||
| CL passive,CPI (L/h) | 7.7 FIXED | — | ||
| Covariates | COV CLR | 1.05 (10) | — | |
| COV ksyn | 0.225 (10) | — | ||
| Residual unexplained variabilities | σ prop – CPI plasma (%) | 18.6 (4) | — | |
| σ add – CPI plasma (nM) | 0.0005 FIXED | — | ||
| σ prop – CPI urine (%) | 47.4 (6) | — | ||
| σ add – CPI urine (nMol) | 0.01 FIXED | — | ||
Parameter estimates in models for PTV (pitavastatin), RIF (rifampin), and CPI (coproporphyrin I) in the healthy population and the population with chronic kidney disease (CKD).
BPV, between‐participant variability; CL active or CL passive , hepatic active or passive uptake clearance (unbound) corrected for hepatocellularity (120 × 106 cells/g of liver); CL B , biliary clearance; CL R , renal clearance; CL RIF , clearance of rifampin; Corr V RIF and CL RIF , correlation between V RIF and CL RIF ; COV CLactive,Gx , a fractional change in CL active in CKD category Gx; COV CLR , power coefficient for CL R of CPI; COV CLrif,BW , continuous covariate (body weight) on CL RIF ; COV ksyn , power coefficient for k syn ; COV Tk0,SEX , categorical covariate (sex) on Tk0 RIF ; COV Vrif,BW , continuous covariate (body weight) on V RIF ; f d1, fractions of Q CO for tissue compartment 1; ka, first‐order absorption rate constant; K i,total , total rifampin inhibition constant for CL active of CPI; K p , tissue partition coefficient; k syn,HV&mild , rate of CPI synthesis in the healthy population and the population with mild CKD; Tk0 RIF,male , duration of zero‐order absorption for male; Tlag RIF , lag time of absorption; V 1_frac , a fraction of V 1 ; V c, volume of central compartment; V RIF , volume of distribution of rifampin; σ add , additive residual error; σ prop , proportional residual error; —, not applicable.
aThe population (fixed effect) parameters and relative standard errors (RSEs, %).
Estimated BPV (%) and its RSE (%).