s-1-(combination) has been researched along with Liver-Diseases* in 2 studies
2 other study(ies) available for s-1-(combination) and Liver-Diseases
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Effect of dimethylnitrosamine-induced liver dysfunction on the pharmacokinetics of 5-fluorouracil after administration of S-1, an antitumour drug, to rats.
The anti-tumour agent S-1 comprises tegafur (a prodrug of 5-fluorouracil; 5-FU), gimeracil (2-chloro-2,4-dihydroxypyridine (CDHP); a competitive inhibitor of 5-FU metabolism) and oteracil potassium. The effect of hepatic dysfunction induced by dimethylnitrosamine (DMN) on the pharmacokinetics of 5-FU after administration of S-1 to rats was investigated.. S-1 (5 mg/kg) was administered intravenously and orally to rats with DMN-induced liver dysfunction. Plasma concentrations of S-1 components and 5-FU were measured by HPLC and LC/MS-MS. Blood tests and in-vitro enzymatic investigations were also conducted.. DMN treatment induced hepatic dysfunction and decreased the conversion of tegafur to 5-FU in the liver without altering renal function or dihydropyrimidine dehydrogenase activity. Following intravenous administration of S-1, the blood concentration-time profiles of CDHP were similar between control rats and rats with hepatic dysfunction, but the half-life of tegafur was significantly prolonged. The maximum plasma concentration (C(max)) of 5-FU was significantly reduced and the area under the blood concentration-time curve (AUC) was reduced by 22%. Following oral administration, the C(max) of tegafur, 5-FU and CDHP were significantly decreased and half-lives significantly increased. Hepatic dysfunction had a less pronounced effect on the AUC of 5-FU (13.6% reduction).. The pharmacokinetic profiles of tegafur, 5-FU and CDHP were altered by changes in the elimination rate of tegafur induced by a decrease in the conversion of tegafur to 5-FU. However, hepatic dysfunction had less of an effect on the AUC of 5-FU, which correlates with anti-tumour effect, after the oral administration of S-1. Topics: Animals; Antineoplastic Agents; Area Under Curve; Chemical and Drug Induced Liver Injury; Dihydrouracil Dehydrogenase (NADP); Dimethylnitrosamine; Drug Combinations; Fluorouracil; Kidney; Liver; Liver Diseases; Male; Oxonic Acid; Rats; Rats, Sprague-Dawley; Tegafur | 2009 |
[A case of unresectable gastric cancer complicated by a serious hepatic disorder and Virchow lymph node metastasis in which FP therapy and TS-1 administration were effective].
The patient was a 65-year-old woman who came to our hospital because she had noticed swelling of a left supraclavicular lymph node. Endoscopy revealed an ulcerous lesion in the L chain region, and poorly differentiated adenocarcinoma of the stomach was diagnosed as a result of a biopsy. Oral therapy was impossible because of pyloric stenosis, and a gastrojejunal bypass operation was performed. Serious hepatic dysfunction occurred postoperatively due to swelling that was suspected of being due to lymph node metastasis in the porta hepatis. For this reason, the TS-1 therapy that had been initially scheduled was abandoned, and low-dose FP therapy was instituted for 4 weeks. Afterward, the swelling resolved and the patient's hepatic disorder and systemic condition improved. Administration of TS-1, 80 mg/day (bid), was started in the outpatient clinic 4 weeks after the completion of FP therapy. Administration had to be discontinued after the first course of TS-1 therapy because of grade 3 thrombocytopenia and neutropenia. However, since marked decreases in tumor markers were observed, TS-1 administration was resumed after recovery. After completion of the second course of TS-1 therapy, a decrease in size of the Virchow lymph node was noted, and PR was diagnosed. TS-1 as initial chemotherapy had to be abandoned for this patient because of a serious hepatic disorder, in which TS-1 administration is contraindicated. However, a favorable response was obtained by concomitant use of FP therapy. Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Liver Diseases; Lymphatic Metastasis; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur | 2002 |