Clinical significance of benzoate-metabolizing capacity in patients with chronic liver disease: pharmacokinetic analysis.
Benzoate-metabolizing capacity was studied in control subjects and in liver disease patients after intra-venous loading of 15 mg benzoate per kg of body weight. In the 7 control subjects, the mean level (+/- SEM) of Cmax for serum benzoate was 104.1 +/- 6.8 micrograms/ml, AUC was 2.57 +/- 0.32 mg.min/ml, MRT was 21.5 +/- 1.5 min and T1/2 was 15.5 +/- 1.3 min. For serum hippurate, on the other hand, Tmax was 27.9 +/- 6.0 min, Cmax was 33.4 +/- 2.1 micrograms/ml, AUC was 1.96 +/- 0.13 mg.min/ml, MRT was 39.6 +/- 2.9 min and T1/2 was 30.7 +/- 2.4 min. In 12 patients with chronic hepatitis, Cmax, AUC, MRT and T1/2 for benzoate and Tmax, MRT and T1/2 for hippurate remained at control levels, but Cmax and AUC for hippurate were slightly decreased compared to controls. However, in 18 patients with liver cirrhosis, Cmax and AUC for benzoate were in the control range but MRT and T1/2 were significantly delayed (p less than 0.01 for both). Moreover, the MRT value was increased in proportion to the severity of liver disease (p less than 0.01). AUC for hippurate was not changed to any extent, and Tmax, MRT and T1/2 were slightly delayed, while Cmax was significantly reduced. AUC, MRT and T1/2 for benzoate and Tmax, MRT and T1/2 for hippurate showed significant correlation with serum albumin levels, prothrombin time and indocyanine green clearance rate. These results suggest that benzoate-metabolizing capacity, especially as indicated by the MRT value for serum benzoate, appears to be a better index than the indocyanine green clearance rate for determining hepatic functional reserve in chronic liver disease.
Yamada
S
S
Second Department of Internal Medicine, Faculty of Medicine, Tottori University, Yonago, Japan.
Yamamoto
T
T
Suou
T
T
Fujii
T
T
Takayama
M
M
Amisaki
T
T
Tabuchi
F
F
Kobayashi
J
J
Hasegawa
M
M
Hoshino
U
U
D000328:Adult; D000368:Aged; D001565:Benzoates / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D019817:Benzoic Acid; D002908:Chronic Disease; D005260:Female; D006505:Hepatitis / Q000378:metabolism; D006626:Hippurates / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D008103:Liver Cirrhosis / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged
D001565:Benzoates; D006626:Hippurates; D019817:Benzoic Acid; C030514:hippuric acid