Skip to main content
. 2013 Sep 27;70(1):65–77. doi: 10.1007/s00228-013-1584-7

Table 3.

Original data estimates and bootstrap average parameter estimates with 95 % confidence intervals

Parameter Unit Original data estimatea Bootstrap average Bootstrap 95 % CIb
 CL/Fn L/h 20.5 20.5 17.3–24.6
 V1/Fn L 105 107 87–136
 Q/Fn L/h 35.8 37.3 21.5–48.5
 V2/Fn L 450 424 297–583
 ka h−1 1.14 1.18 0.80–1.78
 ka, study 2 h−1 0.37 0.38 0.31–0.48
 Lag time h 0.21 0.22 0.20–0.24
 Lag timestudy 2 h 0.82 0.81 0.65–0.90
Covariates on F
  CYP3A5 *1/*3 factor 0.51 0.51 0.42–0.62
 Age and sex
  Fminage, females 0.44 0.43 0.23–0.60
  Fminage, males 0.68 0.66 0.36–0.89
  Fage50 years 44 47 39–70
  HillF age 12.2 14.0 3.5–24.9
 Time, early
  Fmaxearly 1.87 2.04 1.60–3.9
  Fearly50 days 2.6 2.5 1.7–3.0
  HillF early 10.0c 9.4 3.7–10.0c
 Time, late
  Fmaxlate 0.27 0.28 0.14–0.49
  Flate50 days 30 31 24–40
  HillF late 2.3 2.5 1.6–4.7
BSV
 CL/Fn % 33 31 21–40
 V1/Fn % 14 14 0.2–37
 Q/Fn % 91 86 51–114
 V2/Fn % 52 52 32–74
 HillF late % 117 113 78–146
Correlation
 CL/Fn ∼ Q/Fn 0.75 0.74 0.41–0.92
BOV
 Fn % 16 16 13–18
 ka % 63 60 41–84
Residual variability
 Proportional error % 16.7 16.7 15.2–18.4
  Study 2 factor 0.57 0.56 0.41–0.72
  Study 3 factor 0.73 0.72 0.57–0.90

CI, Confidence interval, Fn, bioavailability at baseline nadir (5 days after transplantation); CL/Fn, apparent clearance; V1/Fn, apparent central volume of distribution; Q/Fn, apparent intercompartmental clearance; V2/Fn, apparent peripheral volume of distribution; ka, absorption rate constant; FFM, fat-free mass; Fminage, the minimum value of F at decreasing age relative to reference (male > 60 years); Fage50, the age with half maximum effect on F; HillF age, shape coefficient for the change in F with age; Fmaxearly, the maximum increase in F immediately after transplantation relative to Fn; Fearly50, the day with half maximum early effect on F; HillF early, shape coefficient for the change in F at early time; Fmaxlate, maximum increase in F at later time point, relative to Fn; Flate50, the day with half maximum later effect on F; HillF late, shape coefficient for the change in F at later time; BSV, between subject variability; BOV, between occasion variability

The final model was parameterized as follows: CL/Fn = 20.5 × (FFM /60)3/4 L/h; V1/Fn = 107 × (FFM /60) L; Q/Fn = 37.3 × (FFM /60)3/4 L/h; V2/Fn = 424 × (FFM /60) L

F = [2.04 + (1 − 2.04)/(1 + (TXT/2.5)−9.4)] × [1 + 0.28 / (1+(TXT/31)−2.5)] × [Fminage + (1 − Fminage)/(1 + (AGE/47)−14)] ×  FCYP where Fminage = 0.43 in females and 0.66 in males, FCYP is 0.51 in CYP3A5 expressers and 1 in CYP3A5 nonexpressers and TXT is the time after transplantation in days

aStandardized to 40-year-old male, CYP3A5 nonexpresser with fat-free mass of 60 kg and hematocrit of 45 %, at a time point with the lowest estimated bioavailability (Fn, day 5 post-transplant)

b2.5–97.5 percentile obtained from 500 bootstrap replicates

cUpper bound