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S Chen

Publications and source records attributed to S Chen.

1,625 records · Page 91Linked to original sources
PubMedDate not supplied

Effect of route of administration and biliary excretion on the pharmacokinetics of isotretinoin in the dog.

Oral, intraportal, iv doses of isotretinoin were administered to dogs before and after bile duct cannulation to determine the effect of route of administration and biliary excretion on the pharmacokinetics of this compound. Blood and bile samples were collected and analyzed for isotretinoin using a gradient elution high performance liquid chromatographic method. Blood concentrations were decreased after bile duct cannulation. Decreases in the area under the blood concentration-time curves were greatest following oral dosing, intermediate following intraportal dosing, and least following iv dosing. These results indicate that biliary excretion impacts on the blood profile of isotretinoin as a function of route of administration and that the differences are the result of differences in first pass clearance. In addition, the apparent bioavailability of isotretinoin was 14% in bile cannulated dogs and 54% in the intact (uncannulated) animals, suggesting that enterohepatic recycling of isotretinoin may contribute to its oral bioavailability. Isotretinoin was excreted in the bile; predominantly as a conjugate. The largest percentage (approximately 27%) of the dose was excreted in the bile following intraportal infusion, an intermediate percentage (approximately 8.5%) after iv dosing, and the smallest percentage (approximately 3.3%) after oral dosing. When the amount of drug excreted in bile as intact drug and conjugate is divided by the area under the systemic blood concentration--time curve, the resulting apparent biliary clearances following oral and intraportal administration were almost identical whereas the apparent biliary clearance after iv dosing was substantially less.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMedDate not supplied

Correlation between DNA methylation and pathological changes in human hepatocellular carcinoma.

BACKGROUND/AIMS: This study was undertaken to obtain information at the molecular level on the possible mechanism of human hepatocarcinogenesis and also to provide a clue for further study. METHODOLOGY: We examined the methylation patterns of c-myc and c-N-ras oncogenes, which are most closely related to HCC, by using the Southern blot technique and HpaII/MspI restriction enzymes. In addition, we measured the level of global DNA methylation in cancerous and paracancerous tissues of HCC by incubating DNA with 3H-S-adenosylmethionine (3H-SAM) in the presence of methylase. The measured global level of DNA methylation was compared with pathological changes of the liver. The methylation patterns of oncogenes as well as the levels of global DNA methylation were compared with pathological changes. RESULTS: The results showed that the hypomethylation rates of c-myc and c-N-ras oncogenes were 30% and 61% respectively in human hepatocellular carcinoma, coinciding with a decreased level of global DNA methylation. DNA hypomethylation was highly significant in cases with a tendency of tumor infiltration or metastasis. CONCLUSIONS: It is concluded that abnormal DNA methylation plays an important role in the process of hepatocellular carcinogenesis. DNA methylation level is closely correlated with the biological characteristic of liver cancer, the lower the level of DNA methylation, the stronger the infiltration and metastatic capacity.

Adult↗