Midazolam population pharmacokinetic parameters
Model Parametera | Population Estimate (SEE) | Intersubject Variability (SEE) | Within-Subject Variability (SEE) | |
| Ka (h-1) | 1.3 (7.55) | 54.9 (23) | 38.6 (43) | |
| F2 (oral solution) | 0.32 (4.2) | 34.4 (21) | 16.9 (35) | |
| F1 (tablet) | 0.603 (12.4) | — | — | |
| CLint (l/h) | 63.8 (12) | 77.8 (24) | 19.9 (62) | |
| Effect of Age on CLintb | -7.51 (58) | — | — | |
| Vc (liters) | 38 (7.0) | 35.9 (62) | 52 (29) | |
| Vp (líters) | 18.7 (24) | 43.1 (20) | — | |
| Effect of Weight on Vpc | 1 (22) | — | — | |
| Vt (liters) | 101 (16) | — | — | |
| Effect of Sex on Vtd | -0.318 (44) | — | — | |
| Q1 (l/h) | 97.2 (11) | — | — | |
| Q2 (l/h) | 13.5 (12) | — | — | |
| Covariance between CLint and Vc |
| 0.239 (35) | ||
| Residual errors | ||||
| Proportional error of i.v. | 21.0 (% CV) | |||
| Additive error for i.v. | 0.0468 ng/ml | |||
| Proportional error for oral |
| 35.2 (% CV) | ||
SEE, standard error of the estimate in %; —, not estimated.
↵ a The three-compartment population model (Kramer et al., 1974) was described by a series of differential equations parameterized in terms of Ka, first-order absorption rate constant; Vc, central volume of distribution; Vp and Vt, peripheral volumes of distribution; Q1 and Q2, distributional clearance = intercompartmental flow constant × volume of input compartment; CLint, intrinsic clearance.
↵ b CLint = population CLint - 7.51 · (age/32); CL = Qh · CLint/(Qh + CLint).
↵ c Vp = population Vp · EXP(body weight/72).
↵ d Vt = population Vt · (1 -0.318 · Sex); female = 0, male = 1.