Parameters | Unit | Intra-Arterial | Oral | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
AP | PP | Geometric Mean Ratioa | AP | PP | Geometric Mean Ratio | ||||||
C0/dose | ng/ml/μg | 0.36 ± 0.33 | 0.37 ± 0.16 | 0.81 (0.33–1.99) | N.A. | N.A. | N.A. | ||||
Cmax/dose | ng/ml/mg | N.A. | N.A. | N.A. | 3.52 ± 3.89 | 0.65 ± 0.20 | 3.47 (1.06–11.31)b | ||||
T max | h | N.A. | N.A. | N.A. | 0.25 ± 0.06 | 1.62 ± 0.47 | 0.16 (0.10–0.23)b | ||||
AUC0-∞/dose | h*ng/ml/mg | 0.05 ± 0.02 | 0.09 ± 0.02 | 0.56 (0.39–0.81)b | 3.19 ± 2.20 | 2.04 ± 0.96 | 1.40 (0.61–3.22) | ||||
CL | l/h | 21.1 ± 6.42 | 11.6 ± 2.25 | 1.77 (1.23–2.54)b | N.A. | N.A. | N.A. | ||||
CL | l/h/kg | 2.67 ± 0.76 | 1.62 ± 0.30 | 1.62 (1.15–2.27)b | N.A. | N.A. | N.A. | ||||
CL/F | l/h | N.A. | N.A. | N.A. | 452 ± 284 | 569 ± 232 | 0.71 (0.31–1.64) | ||||
CL/F | l/h/kg | N.A. | N.A. | N.A. | 58.6 ± 39.4 | 80.1 ± 33.4 | 0.65 (0.28–1.54) | ||||
Clf 1′OH MDZc | l/h | 3.13 ± 2.26 | 1.10 ± 0.60 | 2.53 (1.01–6.39)b | 68.3 ± 21.2 | 65.7 ± 15.0 | 1.02 (0.69–1.52) | ||||
Clf 1′OH MDZ | l/h/kg | 0.39 ± 0.29 | 0.15 ± 0.08 | 2.31 (0.98–5.44) | 8.66 ± 2.37 | 9.18 ± 2.11 | 0.93 (0.64–1.36) | ||||
fu | % | 3.65 ± 1.58 | 3.78 ± 0.72 | 0.90 (0.54–1.50) | 3.65 ± 1.58 | 3.78 ± 0.72 | 0.90 (0.54–1.50) | ||||
CLu | l/h | 611 ± 124 | 321 ± 107 | 1.96 (1.34–2.86)b | N.A. | N.A. | N.A. | ||||
CLu | l/h/kg | 78.0 ± 15.3 | 44.6 ± 13.5 | 1.79 (1.25–2.56)b | N.A. | N.A. | N.A. | ||||
CLu/F | l/h | N.A. | N.A. | N.A. | 14,243 ± 8937 | 14,737 ± 4627 | 0.79 (0.31–2.02) | ||||
CLu/F | l/h/kg | N.A. | N.A. | N.A. | 1860 ± 1302 | 2068 ± 683 | 0.72 (0.27–1.90) | ||||
Clf 1′OH MDZ unbound | l/h | 84.6 ± 40.7 | 32.2 ± 24.6 | 2.80 (1.13–6.92)b | 2248 ± 1219 | 1773 ± 450 | 1.13 (0.56–2.27) | ||||
Clf 1′OH MDZ unbound | l/h/kg | 10.6 ± 5.01 | 4.41 ± 3.14 | 2.56 (1.10–5.94)b | 286 ± 153 | 247 ± 57.8 | 1.03 (0.52–2.05) | ||||
V ss | liter | 17.6 ± 5.21 | 11.8 ± 4.52 | 1.55 (0.88–2.73) | N.A. | N.A. | N.A. | ||||
V ss | l/kg | 2.23 ± 0.61 | 1.63 ± 0.57 | 1.41 (0.85–2.35) | N.A. | N.A. | N.A. | ||||
F | % | N.A. | N.A. | N.A. | 7.15 ± 6.62 | 2.38 ± 1.31 | 2.48 (0.95–6.45) | ||||
t 1/2 | h | 1.31 ± 0.36 | 1.17 ± 0.30 | 1.12 (0.78–1.56) | 1.74 ± 0.44 | 1.56 ± 0.44 | 1.14 (0.76–1.70) | ||||
Urinary recoveryd | % | 13.9 ± 6.88 | 8.93 ± 4.20 | 1.48 (0.74–2.99) | 18.6 ± 8.00 | 11.9 ± 4.55 | 1.51 (0.84–2.71) |
fu, percentage unbound in plasma; CLu, unbound plasma clearance; CLu/F, unbound oral plasma clearance; F, bioavailability; t1/2, terminal plasma half-life; N.A., not applicable
↵ a Geometric mean ratio was presented as the ratio of AP/PP with 95% confidence interval in parentheses
↵ b Significantly different antepartum versus postpartum
↵ c Clf 1′-OH MDZ was calculated as the ratio of the amount of MDZ excreted in the 24 h urine as 1′-OH MDZ over MDZ AUC0-∞
↵ d 24-h urinary recovery of the dose as 1′-OH MDZ