Article Figures & Data
Figures
- FIG 1
Semilog scatterplots of plasma drug concentrations versus time since the start of the last dose, stratified by study visit and separated by dose.
- FIG 2
Covariate screening plots. Abbreviations: AGEY, age in years; WTKG, weight in kilograms; HTCM, height in centimeters; ALB, serum albumin concentration in grams per deciliter; BSA, body surface area in square meters; BMI, body mass index in kilograms per square meter; CLCR, creatinine clearance in milliliters per minute per 1.73 m2; CLtu, total clearance of free drug; Vcu, volume of the central compartment for free drug; Vssu, steady-state volume of distribution of free drug.
- FIG 3
Goodness-of-fit plots for the final population PK model. Obs., observed. r2, overall coefficient of determination.
- FIG 4
Precision of the individual clearance estimates from the final population PK model. The vertical band represents the median value (9.15%).
Tables
- TABLE 1
Subject demographic characteristics of the PK analysis population
Variable 100-mg group (n = 64) 150-mg group (n = 65) All patients (n = 129) No. (%) Mean no. (CV [%]) Median (min-max) No. (%) Mean no. (CV [%]) Median (min-max) No. (%) Mean no. (CV [%]) Median (min-max) Age (yr) 41.3 (12.7) 41.0 (18.0–73.0) 42.0 (13.4) 42.0 (20.0–73.0) 41.6 (13.0) 41.0 (18.0–73.0) Wt (kg) 89.0 (20.6) 85.1 (43.8–146) 95.6 (23.4) 89.1 (46.4–161) 92.3 (22.2) 87.5 (43.8–161) Ht (cm) 173 (10.5) 174 (152–191) 173 (9.70) 173 (150–196) 173 (10.0) 173 (150–196) BSA (m2) 2.07 (0.258) 2.04 (1.51–2.71) 2.15 (0.286) 2.10 (1.41–2.81) 2.11 (0.274) 2.05 (1.41–2.81) BMI (kg/m2) 30.0 (7.53) 29.2 (12.1–53.7) 32.1 (7.82) 31.4 (19.4–55.5) 31.1 (7.73) 30.3 (12.1–55.5) CLCR (ml/min/1.73 m2) 122 (33.3) 118 (49.6–207) 114 (32.5) 113 (35.6–181) 118 (33.0) 117 (35.6–207) Serum albumin level (g/liter) 42.1 (4.62) 42.0 (28.0–52.0) 41.6 (4.47) 42.0 (29.0–50.0) 41.9 (4.54) 42.0 (28.0–52.0) No. (%) of males 43 (67.2) 43 (66.2) 86 (66.7) No. (%) of females 21 (32.8) 22 (33.9) 43 (33.3) No. (%) of Caucasians 52 (81.3) 45 (69.2) 97 (75.2) No. (%) of blacks 7 (10.9) 13 (20.0) 20 (15.5) No. (%) of Asians 0 1 (1.54) 1 (0.775) No. (%) of Native American/Alaskan Natives 2 (3.13) 4 (6.15) 6 (4.65) No. (%) of Native Hawaiians/Pacific Islanders 2 (3.13) 2 (3.08) 4 (3.10) No. (%) of mixed race 1 (1.56) 0 1 (0.775) - TABLE 2
Final population PK model parameter estimates and standard errors
Parametera Final estimated mean value (% SEM) Population mean Magnitude of interindividual variability (CV %) Vcu (liters) 66.1 (18.6) 139 (29.4) Vp1u (liters) 582 (7.51) 48.0 (17.3) CLd1u (liters/h) 60.8 (11.0) 35.1 (30.4) Vp2u (liters) 211 (10.2) 64.5 (19.0) CLd2u (liters/h) 199 (10.1) 39.3 (25.8) CLtu (liters/h) 120 (4.04) 17.8 (14.4) Bmax 12.7 KD 2.07 SDin 0.0005 SDsl 0.217 (2.62) ↵a Volumes and clearances are scaled to free-drug concentrations. The minimum value of the objective function is −1,888. Vp1u, volume of distribution of the first peripheral compartment; Vp2u, volume of distribution of the second peripheral compartment; CLd2u, second distributional clearance; Bmax, parameter describing the maximum extent of protein binding; SDin, intercept (additive) term for residual variability model for plasma concentrations; SDsl, slope (proportional) term for residual variability model.
- TABLE 3
Summary statistics for BC-3781 PK exposure estimates and half-life
Parameter and dose (mg) Mean (SD) Median (min, max) Day 1 Cmax (μg/ml) 100 1.57 (0.974) 1.46 (0.515, 8.11) 150 1.90 (0.705) 1.88 (0.633, 4.38) Day 1 AUC0–24 (μg · h/ml) 100 10.9 (5.97) 9.87 (3.86, 48.3) 150 14.1 (5.76) 12.8 (4.29, 35.1) Half-life (h) 100 11.0 (5.18) 9.74 (0.838, 23.5) 150 13.2 (5.79) 12.4 (3.38, 23.5)
