Novel Galactose Single Point Method as a Measure of Residual Liver Function: Example of Cefoperazone Kinetics in Patients with Liver Cirrhosis

Hu, Oliver Yoa Pu; Tang, Haoning; Chang, Ching‐Ling ‐L

doi:10.1002/j.1552-4604.1995.tb04055.x

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…However, they often lack sensitivity in the early stages of liver diseases and change only in advanced stages. The galactose single-point (GSP) method has been recommended by the US Food and Drug Administration in the guidance document for the industry, "Pharmacokinetics in Patients with Impaired Hepatic Function: Study Design, Data Analysis, and Impact on Dosing and Labeling," and has been successfully used to predict a variety of liver diseases (31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Kaempferol on Isoniazid- and Rifampicin-Induced Hepatotoxicity

Shih

Young

Lee

et al. 2013

AAPS J

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Abstract. Isoniazid (INH) and rifampicin (RIF) are the first-line drugs for antituberculosis (anti-TB) chemotherapy. The levels of serum transaminases [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)] are abnormal in 27% of patients undergoing INH and RIF treatments and in 19% of patients undergoing treatment with INH alone. Cytochrome P450 2E1 (CYP2E1) metabolizes many toxic substrates, including ethanol, carbon tetrachloride, and INH, which ultimately results in liver injury. The objective of this study was to screen for CYP2E1 inhibitors in vitro and investigate whether the selected compound could prevent INH/RIF-induced hepatotoxicity in vivo. We screened 83 known compounds from food and herbal medicines as inhibitors of CYP2E1. The hepatotoxic dose of INH/RIF was 50/100 mg kg −1 day −1 . Hepatotoxicity was assessed using galactose single-point (GSP) method (a quantitative measurement of liver function), histopathological examination of the liver, malondialdehyde (MDA) assay, and measurement of AST and ALT activities. Kaempferol inhibited CYP2E1 activity in mice by 0.31-to 0.48-fold (p<0.005). Mice with INH/RIF-induced hepatotoxicity showed significantly abnormal serum levels of AST and ALT, and GSP value, and these values could be decreased by the administration of kaempferol (p<0.005). Kaempferol significantly reduced the depletion of hepatic glutathione and prevented the increase in MDA formation in mice. Furthermore, kaempferol did not affect the anti-TB effects of INH/RIF. To our knowledge, this is the first report of kaempferol's utility as an adjuvant for preventing CYP2E1-mediated hepatotoxicity induced by drugs such as INH and RIF.

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Section: Introductionmentioning

confidence: 99%

Protective Effects of Kaempferol on Isoniazid- and Rifampicin-Induced Hepatotoxicity

Shih

Young

Lee

et al. 2013

AAPS J

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“…This GSP method has been successfully applied to drugs which are extensively metabolized or excreted from the liver, such as promazine and cefoperazone clearance in patients with various liver diseases (Hu et al 1994(Hu et al , 1995b. This method has also been recommended by the US Food and Drug Administration (FDA) in the guidance for industry pharmacokinetics in patients with impaired hepatic function (FDA 2003).…”

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confidence: 99%

Quantitative rat liver function test by galactose single point method

et al. 2008

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SummaryThe purpose of this study was to investigate the galactose single point (GSP) method, a residual liver function test recently recommended by the US Food and Drug Administration, which can be a useful tool for rat liver function measurement. Rats were treated either with carbon tetrachloride (CCl 4 ) alone (1 mL/kg, intraperitoneally [i.p.]) for one day or with isoniazid (INH) alone (150 mg/kg, i.p.) or (in order to ameliorate the effects of INH) with a combination of INH and bis-p-nitrophenyl phosphate (BNPP) (25 mg/kg, i.p.) for 21 days. Hepatotoxicity was assayed by plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities and scores of histological activity index-necroinflammation (HAI-NI) of the respective liver specimens. The GSP method in rats was defined by the galactose blood level after 60 min. Significant differences in GSP values were observed between controls and the CCl 4 -treated rats. After 21 days of treatment, no significant changes in AST and ALT values were observed among the control, INH and INH-BNPP groups. There were significant differences in average GSP values for controls (P , 0.001) and INH-BNPP (P , 0.001) compared with INH alone. Highly significant correlations (P , 0.001) were obtained between GSP and scores of HAI-NI for all the groups. GSP was concluded to be a more sensitive biomarker of INH-induced hepatotoxicity than AST or ALT in the rats. The GSP method has been proved to be a simple and useful tool for the quantitative determination of liver function in rats, which can possibly be extended to other animals.

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“…A maximum 10% CV was permitted. The slope and intercept of the calibration curves were also checked on a daily basis [13]. …”

Section: Methodsmentioning

confidence: 99%

Long-Term and Short-Term Effects of Hemodialysis on Liver Function Evaluated Using the Galactose Single-Point Test

Hou

Liu

Liao

et al. 2014

The Scientific World Journal

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Aim. The galactose single-point (GSP) test assesses functioning liver mass by measuring the galactose concentration in the blood 1 hour after its administration. The purpose of this study was to investigate the impact of hemodialysis (HD) on short-term and long-term liver function by use of GSP test. Methods. Seventy-four patients on maintenance HD (46 males and 28 females, 60.38 ± 11.86 years) with a mean time on HD of 60.77 ± 48.31 months were studied. The GSP values were compared in two groups: (1) before and after single session HD, and (2) after one year of maintenance HD. Results. Among the 74 HD patient, only the post-HD Cr levels and years on dialysis were significantly correlated with GSP values (r = 0.280, P < 0.05 and r = −0.240, P < 0.05, resp.). 14 of 74 patients were selected for GSP evaluation before and after a single HD session, and the hepatic clearance of galactose was similar (pre-HD 410 ± 254 g/mL, post-HD 439 ± 298 g/mL, P = 0.49). GSP values decreased from 420.20 ± 175.26 g/mL to 383.40 ± 153.97 g/mL after 1 year maintenance HD in other 15 patients (mean difference: 19.00 ± 37.66 g/mL, P < 0.05). Conclusions. Patients on maintenance HD for several years may experience improvement of their liver function. However, a single HD session does not affect liver function significantly as assessed by the GSP test. Since the metabolism of galactose is dependent on liver blood flow and hepatic functional mass, further studies are needed.

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Novel Galactose Single Point Method as a Measure of Residual Liver Function: Example of Cefoperazone Kinetics in Patients with Liver Cirrhosis

Cited by 12 publications

References 26 publications

Protective Effects of Kaempferol on Isoniazid- and Rifampicin-Induced Hepatotoxicity

Protective Effects of Kaempferol on Isoniazid- and Rifampicin-Induced Hepatotoxicity

Quantitative rat liver function test by galactose single point method

Long-Term and Short-Term Effects of Hemodialysis on Liver Function Evaluated Using the Galactose Single-Point Test

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