| Parameter description . | Typical value (95% CI)a . |
|---|---|
| Clearance, (L/h)b | 11.5 (10.5–12.5) |
| Central volume of distribution, Vc (L)b | 262 (178–375) |
| Intercompartmental clearance, Q1 (L/h)b | 56.3 (49.6–62.6) |
| Peripheral volume 1, Vp1 (L)b | 10 500 (9320–11 600) |
| Intercompartmental clearance, Q2 (L/h)b | 86 (74.6–99.5) |
| Peripheral volume 2, Vp2 (L)b | 889 (696–1070) |
| Absorption mean transit time (h) | 1.41 (1.10–1.67) |
| Number of transit compartments (NN) | 4.75 (3.01–7.65) |
| Absorption rate constant, Ka (1/h) | 0.209 (0.175–0.261) |
| Relative bioavailability baseline | 0.685 (0.615–0.771) |
| Bioavailability, F | 1 [FIXED] |
| Proportional error (%) | 11.4 (10.8–12.1) |
| Additive error (mg/L)c | 0.00156 [FIXED] |
| Additive error (PROBeX sparse data) (mg/L) | 0.0905 (0.077–0.107) |
| P-glycoprotein inhibition half-life (days)d | 1.44 (0.683–2.85) |
| Between-subject variability (%)e | |
| clearance | 25.6 (17–33.5) |
| central volume | 23.5 (8.39–35.1) |
| peripheral volume 1 | 29.6 (20.4–38.1) |
| peripheral volume 2 | 54.6 (42.3–73.9) |
| bioavailability | 30.1 (25.2–35.5) |
| Between-occasion variability (%)e | |
| absorption mean transit time | 46.6 (38.1–56.9) |
| absorption rate constant | 32.6 (27.1–38) |
| bioavailability | 35.4 (31.8–39.6) |
| Terminal half-life (days)f | |
| median patient | 34.2 |
| female | 49.5 |
| male | 21.8 |
| Parameter description . | Typical value (95% CI)a . |
|---|---|
| Clearance, (L/h)b | 11.5 (10.5–12.5) |
| Central volume of distribution, Vc (L)b | 262 (178–375) |
| Intercompartmental clearance, Q1 (L/h)b | 56.3 (49.6–62.6) |
| Peripheral volume 1, Vp1 (L)b | 10 500 (9320–11 600) |
| Intercompartmental clearance, Q2 (L/h)b | 86 (74.6–99.5) |
| Peripheral volume 2, Vp2 (L)b | 889 (696–1070) |
| Absorption mean transit time (h) | 1.41 (1.10–1.67) |
| Number of transit compartments (NN) | 4.75 (3.01–7.65) |
| Absorption rate constant, Ka (1/h) | 0.209 (0.175–0.261) |
| Relative bioavailability baseline | 0.685 (0.615–0.771) |
| Bioavailability, F | 1 [FIXED] |
| Proportional error (%) | 11.4 (10.8–12.1) |
| Additive error (mg/L)c | 0.00156 [FIXED] |
| Additive error (PROBeX sparse data) (mg/L) | 0.0905 (0.077–0.107) |
| P-glycoprotein inhibition half-life (days)d | 1.44 (0.683–2.85) |
| Between-subject variability (%)e | |
| clearance | 25.6 (17–33.5) |
| central volume | 23.5 (8.39–35.1) |
| peripheral volume 1 | 29.6 (20.4–38.1) |
| peripheral volume 2 | 54.6 (42.3–73.9) |
| bioavailability | 30.1 (25.2–35.5) |
| Between-occasion variability (%)e | |
| absorption mean transit time | 46.6 (38.1–56.9) |
| absorption rate constant | 32.6 (27.1–38) |
| bioavailability | 35.4 (31.8–39.6) |
| Terminal half-life (days)f | |
| median patient | 34.2 |
| female | 49.5 |
| male | 21.8 |
95% CI obtained with the sampling importance resampling technique using PsN software.
Allometric scaling used for CL, Vc, Vp1, Vp2, Q1 and Q2; typical values reported for the median weight (55 kg), FFM (42 kg) and fat mass (13 kg) as reported in Table 1.
Estimate of the additive error was not statistically significant from the lower bound (LLOQ/2) and was thus fixed to that value.
Inhibitory effect of clofazimine on P-glycoprotein using an exponential maturation function (described in the Supplementary data).
Between-subject variability and between-occasion variability were assumed to be log-normally distributed and reported as approximate %CV.
Derived parameters outside the estimation software: calculated for the typical male and female median values as reported in Table 1.
| Parameter description . | Typical value (95% CI)a . |
|---|---|
| Clearance, (L/h)b | 11.5 (10.5–12.5) |
| Central volume of distribution, Vc (L)b | 262 (178–375) |
| Intercompartmental clearance, Q1 (L/h)b | 56.3 (49.6–62.6) |
| Peripheral volume 1, Vp1 (L)b | 10 500 (9320–11 600) |
| Intercompartmental clearance, Q2 (L/h)b | 86 (74.6–99.5) |
| Peripheral volume 2, Vp2 (L)b | 889 (696–1070) |
| Absorption mean transit time (h) | 1.41 (1.10–1.67) |
| Number of transit compartments (NN) | 4.75 (3.01–7.65) |
| Absorption rate constant, Ka (1/h) | 0.209 (0.175–0.261) |
| Relative bioavailability baseline | 0.685 (0.615–0.771) |
| Bioavailability, F | 1 [FIXED] |
| Proportional error (%) | 11.4 (10.8–12.1) |
| Additive error (mg/L)c | 0.00156 [FIXED] |
| Additive error (PROBeX sparse data) (mg/L) | 0.0905 (0.077–0.107) |
| P-glycoprotein inhibition half-life (days)d | 1.44 (0.683–2.85) |
| Between-subject variability (%)e | |
| clearance | 25.6 (17–33.5) |
| central volume | 23.5 (8.39–35.1) |
| peripheral volume 1 | 29.6 (20.4–38.1) |
| peripheral volume 2 | 54.6 (42.3–73.9) |
| bioavailability | 30.1 (25.2–35.5) |
| Between-occasion variability (%)e | |
| absorption mean transit time | 46.6 (38.1–56.9) |
| absorption rate constant | 32.6 (27.1–38) |
| bioavailability | 35.4 (31.8–39.6) |
| Terminal half-life (days)f | |
| median patient | 34.2 |
| female | 49.5 |
| male | 21.8 |
| Parameter description . | Typical value (95% CI)a . |
|---|---|
| Clearance, (L/h)b | 11.5 (10.5–12.5) |
| Central volume of distribution, Vc (L)b | 262 (178–375) |
| Intercompartmental clearance, Q1 (L/h)b | 56.3 (49.6–62.6) |
| Peripheral volume 1, Vp1 (L)b | 10 500 (9320–11 600) |
| Intercompartmental clearance, Q2 (L/h)b | 86 (74.6–99.5) |
| Peripheral volume 2, Vp2 (L)b | 889 (696–1070) |
| Absorption mean transit time (h) | 1.41 (1.10–1.67) |
| Number of transit compartments (NN) | 4.75 (3.01–7.65) |
| Absorption rate constant, Ka (1/h) | 0.209 (0.175–0.261) |
| Relative bioavailability baseline | 0.685 (0.615–0.771) |
| Bioavailability, F | 1 [FIXED] |
| Proportional error (%) | 11.4 (10.8–12.1) |
| Additive error (mg/L)c | 0.00156 [FIXED] |
| Additive error (PROBeX sparse data) (mg/L) | 0.0905 (0.077–0.107) |
| P-glycoprotein inhibition half-life (days)d | 1.44 (0.683–2.85) |
| Between-subject variability (%)e | |
| clearance | 25.6 (17–33.5) |
| central volume | 23.5 (8.39–35.1) |
| peripheral volume 1 | 29.6 (20.4–38.1) |
| peripheral volume 2 | 54.6 (42.3–73.9) |
| bioavailability | 30.1 (25.2–35.5) |
| Between-occasion variability (%)e | |
| absorption mean transit time | 46.6 (38.1–56.9) |
| absorption rate constant | 32.6 (27.1–38) |
| bioavailability | 35.4 (31.8–39.6) |
| Terminal half-life (days)f | |
| median patient | 34.2 |
| female | 49.5 |
| male | 21.8 |
95% CI obtained with the sampling importance resampling technique using PsN software.
Allometric scaling used for CL, Vc, Vp1, Vp2, Q1 and Q2; typical values reported for the median weight (55 kg), FFM (42 kg) and fat mass (13 kg) as reported in Table 1.
Estimate of the additive error was not statistically significant from the lower bound (LLOQ/2) and was thus fixed to that value.
Inhibitory effect of clofazimine on P-glycoprotein using an exponential maturation function (described in the Supplementary data).
Between-subject variability and between-occasion variability were assumed to be log-normally distributed and reported as approximate %CV.
Derived parameters outside the estimation software: calculated for the typical male and female median values as reported in Table 1.
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