The effect of transcatheter arterial chemoembolization on CYP1A2 activity in patients with hepatocellular carcinoma.
OBJECTIVE
CYP1A2, a constitutive enzyme expressed in the liver, is among the phase I enzymes responsible for polycyclic aromatic hydrocarbons metabolism. Phenacetin O-de-ethylation is a marker for CYP1A2 activity. This study investigates the metabolism of phenacetin in patients with hepatocellular carcinoma (HCC).


METHODS
The phenacetin test was performed in 56 normal subjects and 92 HCC patients. The test was repeated in HCC patients after treatment with transcatheter arterial chemoembolization (TACE). The recovery of phenacetin's urinary metabolites was studies in 12 normal subjects and 14 patients with HCC.


RESULTS
Compared with normal controls, the recovery of phenacetin O-de-ethylated metabolites decreased by 42.5% (P < 0.01) in patients with HCC and diminished further after TACE (P < 0.05). The ratio of plasma total paracetamol to phenacetin was much lower than in normal controls (P < 0.01) and was reduced by 40.7% more after TACE (P < 0.05).


CONCLUSIONS
The metabolism of phenacetin is impaired in patient with HCC. TACE damages the activity of CYP1A2. The phenacetin test can be used to predict effect of TACE on liver function in HCC patients.
Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
W
W
Huang
Z-Q
ZQ
Qu
X-D
XD
Li
P
P
He
N
N
Ding
S-L
SL
Zhang
M C
MC
Wu
D000082:Acetaminophen / Q000493:pharmacokinetics; D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000473:pathology / Q000628:therapy*; D016461:Chemoembolization, Therapeutic / Q000009:adverse effects*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D008111:Liver Function Tests / Q000379:methods; D008113:Liver Neoplasms / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010615:Phenacetin / Q000493:pharmacokinetics
D000082:Acetaminophen; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D010615:Phenacetin