Single plasma sampling to predict oral clearance of CYP3A probe midazolam
Abstract
Aim: To find out a single plasma sampling to estimate oral clearance of midazolam (MDZ) and CYP3A activity, and explore the pharmacokinetics of midazolam hydroxylation in Chinese subjects.
Methods: The pharmacokinetics of midazolam was assessed in ten healthy male individuals after an oral dose of 7.5 mg midazolam.
Results: A significant correlation (r = 0.7, P < 0.05, n = 10) was found between plasma MDZ clearance and the plasma ratio of 1'-hydroxymidazolam to midazolam, which was assessed at 1 h after MDZ intake in the volunteers. Pharmacokinetics parameters of midazolam were as follows: Cmax (191 +/- 17) nmol/L, tmax (1.01 +/- 0.14) h, t(1/2) (3.2 +/- 0.4) h, AUC(0-infinity) (681 +/- 43) nmol.h.L-1), Cl(oral) (0.54 +/- 0.04) L.h-1.kg-1, Ke (0.2415 +/- 0.0021) h-1, Kalpha (0.82 +/- 0.18) h-1.
Conclusion: Single plasma sampling of 1 h after 7.5 mg oral MDZ intake can be used to predict the oral clearance of midazolam.
Keywords:
Methods: The pharmacokinetics of midazolam was assessed in ten healthy male individuals after an oral dose of 7.5 mg midazolam.
Results: A significant correlation (r = 0.7, P < 0.05, n = 10) was found between plasma MDZ clearance and the plasma ratio of 1'-hydroxymidazolam to midazolam, which was assessed at 1 h after MDZ intake in the volunteers. Pharmacokinetics parameters of midazolam were as follows: Cmax (191 +/- 17) nmol/L, tmax (1.01 +/- 0.14) h, t(1/2) (3.2 +/- 0.4) h, AUC(0-infinity) (681 +/- 43) nmol.h.L-1), Cl(oral) (0.54 +/- 0.04) L.h-1.kg-1, Ke (0.2415 +/- 0.0021) h-1, Kalpha (0.82 +/- 0.18) h-1.
Conclusion: Single plasma sampling of 1 h after 7.5 mg oral MDZ intake can be used to predict the oral clearance of midazolam.