Table 1.
Pharmacokinetics of fosmidomycin analysed by model-independent and model-dependent approach in patients with sensitive responses in Group-I and II.
| Pharmacokinetic Parameters | Model-independent | Model-dependent | ||
|
Group-I (n = 23) |
Group-II (n = 45) |
Group-I (n = 23) |
Group-II (n = 45) |
|
| tmax (hr) | 2.0 (1.0–4.0) | 3.0 (1.0–6.0) | 2.6 (1.0–3.8)a | 3.2 (0.8–4.3) |
| tlag (hr) | NA | NA | 0.3 (0.001–0.8) | 0.55 (0.001–1.6) |
| K01 (/hr) | NA | NA | 0.35 (0.15–3.00) | 0.56 (0.09–4.00) |
| t1/2a (hr) | NA | NA | 2.0 (0.2–8.0) | 1.97 (0.1–7.7) |
| Cmax (μg/ml) | 2.41 (0.91–16.23)b | 3.74(1.49–8.94) | 1.77 (0.96–2.97)c | 2.92 (1.40–6.93) |
| AUC (μg.hr/ml) | 10.63 (4.27–53.85) | 23.31 (11.42–66.13) | 13.30 (6.89–24.33)d | 26.18 (14.72–54.49) |
| K10 (/hr) | NA | NA | 0.37 (0.09–1.92) | 0.36 (0.08–2.00) |
| t1/2z (hr) | 3.5 (0.8–14.9)e | 4.2 (2.1–7.9) | NA | NA |
| t1/2e (hr) | NA | NA | 1.6 (0.2–5.3)f | 2.2 (0.3–8.2) |
| CL/F (l/hr) | 47.51 (16.46)g | 57.69 (9.29–132.54) | 67.62 (23.39–130.57) | 68.27 (33.03–122.31) |
| Vz/F (l) | 272.64 (20.22–702.25)h | 338.56 (131.65–895.17) | NA | NA |
| V/F (l) | NA | NA | 194.50 (34.17–855.40) | 174.11 (30.23–924.62) |
| Cmin-ss (μg/ml) | 1.37 (1.08–5.09)i | 0.80 (0.20–2.11) | 1.62 (0.66–2.69)j | 0.97 (0.20–2.25) |
| Cmax-ss (μg/ml) | 2.28 (1.34–9.43)k | 2.80 (1.18–6.52) | 2.63 (1.46–4.64)l | 3.26 (1.83–7.27) |
| Cave-ss (μg/ml) | 1.77 (0.71–8.98) | 1.94 (0.95–5.51) | 2.22(1.45–4.06) | 2.18(0.51–4.54) |
| Cmax-min-ss (μg/ml) | 0.71 (0.05–4.34)m | 2.03 (0.59–5.41) | 1.11 (0.39–2.23)n | 2.24 (0.04–5.76) |
| Fluctuation (%) | 41.9 (40.1–203.6)° | 110.0 (30.8–223.4) | 49.2 (50.8–191.5)p | 118.7 (41.2–218.5) |
Data are presented as median (95% CI).
NA = Not applicable
a Statistically significant difference from Group-II with p = 0.009, 95%CI = 0.9 (0.2–1.5); b p = 0.029, 95%CI = 1.45(0.77–2.04); c p < 0.0001, 95%CI = 0.78(0.15–2.11); d p < 0.0001, 95%CI = 15.99(4.15–26.77); e p = 0.022, 95%CI = 0.8(0.4–6.5),;f p < 0.0001, 95%CI = 0.2(0.09–0.9); g p = 0.006, 95%CI = 14.77(6.11–122.14); h p = 0.0001, 95%CI = 76.66(33.48–48.77); i p = 0.0001, 95%CI = 0.78(0.34–2.25); j p < 0.0001, 95%CI = 0.32(0.11–1.02); k p = 0.048, 95%CI = 0.45(0.20–0.79); l p ≤ 0.0001, 95%CI = 0.98(0.45–1.45); m p = 0.033, 95%CI = 0.64(0.23–1.78); n p = 0.039, 95%CI = 0.67(0.23–1.12); ° p = 0.001, 95%CI-65.8(23.1–102.3); p p = 0.0001, 95%CI = 62.1(24.6–123.6) (Mann-Whitney U-test)