Single plasma sampling to predict oral clearance of CYP3A probe midazolam.
OBJECTIVE
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.


CONCLUSIONS
Single plasma sampling of 1 h after 7.5 mg oral MDZ intake can be used to predict the oral clearance of midazolam.
Zhu
B
B
Pharmacogenetics Research Institute, Hunan Medical University, Changsha 410078, China.
Ou-Yang
D S
DS
Cheng
Z N
ZN
Huang
S L
SL
Zhou
H H
HH
D000284:Administration, Oral; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008874:Midazolam / Q000097:blood / Q000493:pharmacokinetics*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*
D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D008874:Midazolam