Pharmacokinetic modulation of irinotecan metabolites by sulphobromophthalein in rats

The Journal of Pharmacy and Pharmacology
Tatsuya ItohKen Iseki

Abstract

The purpose of this study was to modulate the pharmacokinetics of irinotecan metabolites, SN-38 and SN-38-glucuronide, by possibly reducing biliary excretion, which in turn could lower irinotecan toxicity. SN-38-glucuronide is associated with severe diarrhoea that occurs after irinotecan therapy as a result of enteric injury caused by SN-38. Sulphobromophthalein is used clinically as a drug for testing liver function and is considered to be a safe drug. We investigated the effect of sulphobromophthalein on the disposition of irinotecan metabolites after CPT-11 (7-ethyl-10-[10-4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin) administration. Wistar rats were administered CPT11 (500 microg/body) in saline as a bolus injection into the femoral vein through a catheter. The volume of drug solution injected into each animal was 1 mL. Rats were either administered CPT-11 alone or simultaneously with sulphobromophthalein (20 mg/body). After administration, blood and bile samples were taken at appropriate intervals and analysed by HPLC. Co-administration of sulphobromophthalein partially inhibited the biliary excretion of SN-38-glucuronide with a concomitant increase in its area under the plasma concentration-time curve (AUC) but...Continue Reading

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Citations

Nov 27, 2004·Cancer Chemotherapy and Pharmacology·Tatsuya ItohKen Iseki
Feb 16, 2005·Cancer Chemotherapy and Pharmacology·Shirou ItagakiKen Iseki
May 3, 2008·Biological & Pharmaceutical Bulletin·Jiro OguraKen Iseki
May 13, 2010·Biological & Pharmaceutical Bulletin·Jiro OguraKen Iseki
Mar 5, 2011·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Jiro OguraKen Iseki
Sep 19, 2012·Drug Metabolism and Pharmacokinetics·Masahiro SegawaKen Iseki
Aug 9, 2005·European Journal of Pharmacology·Shirou ItagakiKen Iseki
Aug 19, 2004·The Journal of Pharmacology and Experimental Therapeutics·Shirou ItagakiKen Iseki
Jul 2, 2021·Journal of Pharmaceutical Health Care and Sciences·Toshiaki TsuchitaniHisakazu Ohtani
Aug 10, 2005·Biochimica Et Biophysica Acta·Masaki KobayashiKen Iseki

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