Pharmacokinetic parameters of blebbistatin, NBleb, and AmBleb from experiments using rat and human hepatocytes
Clint = (ln2/t1/2) × ((cell number/tissue weight)/(cell number/incubation volume)) × (liver weight/body weight), where t1/2 is the time required to achieve 50% of the initial concentration at t = 0 min. ClH = (Clint × fu × HPF)/(Clint × fu + HPF), where HPF = QH × plasma/blood ratio, where QH = 55.2 ml/min per kilogram for rat, 20.7 ml/min per kilogram for human, plasma/blood ratio = 0.63 for rat, 0.57 for human. EH = ClH/QH. F (bioavailability) = 100*(1−EH).
Substance | t1/2 (min) | Clint (ml/min per kilogram) | ClH (ml/min per kilogram) | EH | F (%) |
---|---|---|---|---|---|
Rat | |||||
Blebbistatin | 20.17 | 80.41 | 22.62 | 0.41 | 59.02 |
NBleb | 114.30 | 14.19 | 10.08 | 0.18 | 81.74 |
AmBleb | 18.98 | 85.46 | 24.08 | 0.44 | 56.38 |
Human | |||||
Blebbistatin | 26.13 | 43.72 | 8.84 | 0.43 | 57.31 |
NBleb | 20.31 | 56.25 | 9.75 | 0.47 | 52.88 |
AmBleb | 52.15 | 21.91 | 7.43 | 0.36 | 64.11 |