AUCpo the plasma-concentration-time curve of following an oral
administration
CLh hepatic clearance
CLint intrinsic clearance
CL
0
int intrinsic clearance determinedin vitro
CLr renal clearance
CLT total body clearance
CYP cytochrome P450
DMSO dimethyl sulfoxide
Eh hepatic extraction
Fh hepatic bioavailability
ESI electrospray ionization
FL fluorescence
FMO flavin-containing monooxygenases
HTS high-throughput screening
fa the fraction absorbed in the intestinal tract
fu unbound fraction
fu
0
the unbound fraction in thein vitrometabolic systemsGlc-6-PO 4 glucose-6-phosphate
G6PDH glucose-6-phosphate dehydrogenase
GSH glutathione (reduced form)
HLM human liver microsomal preparations
HTS high-throughput screening
IS internal standard
kcat the maximal catalytic rate constant
ke the elimination rate constant
Km Michaelis constant, or the substrate concentration at half
maximum rate
LC/MS/MS liquid chromatography-triple quadrupole mass spectrometry
MeOH methanol
MRM multiple reaction monitoring
NADH b-nicotinamide adenine dinucleotide (reduced form)
NADPH b-nicotinamide adenine dinucleotide phosphate (reduced form)
NCE new chemical entity
PBS phosphate-buffered saline
PK pharmacokinetics
Qh hepatic flow rate
SF scaling factor
t1/2 half-life
440 DETERMINATION OF METABOLIC RATES AND ENZYME KINETICS