Biotransformation of the antiemetic 5-HT3 antagonist tropisetron in liver and kidney slices of human, rat and dog with a comparison to in vivo

European Journal of Drug Metabolism and Pharmacokinetics

Volumn 21, Issue 1, 1996, Pages 43-50

  Vickers, A E M ^a   Fischer, V ^a   Connors, M S ^b   Biggi, W A ^a   Heitz, F ^a   Baldeck, J P ^a   Brendel, K ^b  

^a Sandoz Pharma Ltd   (Switzerland)

^b UNIVERSITY OF ARIZONA   (United States)

Author keywords

Biotransformation; Dog; Human; Kidney slices; Liver slices; Rat; Tropisetron

Indexed keywords

DRUG METABOLITE; TROPISETRON;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; DOG; DRUG BIOAVAILABILITY; DRUG BLOOD LEVEL; DRUG METABOLISM; DRUG TRANSFORMATION; DRUG URINE LEVEL; HUMAN; HUMAN EXPERIMENT; HUMAN TISSUE; JEJUNUM; KIDNEY CLEARANCE; KIDNEY SLICE; LIVER METABOLISM; LIVER SLICE; MALE; NONHUMAN; NORMAL HUMAN; ORAL DRUG ADMINISTRATION; RAT; SPECIES DIFFERENCE;

EID: 0030036901     PISSN: 03787966     EISSN: None     Source Type: Journal    
DOI: 10.1007/BF03190277     Document Type: Article

References (19)

1. Richardson B.P., Engel G., Donatsch P., Stadler P.A. (1985) : Identification of serotonin M-receptor subtypes and their specific blockade by a new class of drugs. Nature, 316, 126-131
2. Round A., Wallis D.I. (1986) : The depolarizing action of 5-hydroxytryptamine on rabbit vagal afferent and sympathetic neurones in vitro and its selective blockade by ICS 205-930. Br J Pharmacol., 88, 485-494.
3. 3 receptors mediate cytotoxic drug and radiation-invoked emesis. Br. J. Cancer, 56, 159-162.
4. 3H]-ICS 205-930. J. Receptor Res., 9, 65-79.
5. Tyers M.B., Bunce K.T., Humphrey P.P.A. (1989) : Pharmacological and anti-emetic properties of ondansetron. Eur J. Cancer Clin. Oncol., 25, S15-S19.
6. Bregni M, Siena S., Di Nicola M., Bonadonna G., Gianni A.M. (1991) : Tropisetron plus haloperidol to ameliorate nausea and vomiting associated with high-dose alkylating agent cancer chemotherapy. Eur. J. Cancer, 27, 561-565.
7. Kris M.G., Tyson L.B., Gralia R.J., et al. (1983) : Extrapyramidal reactions with high-dose metoclopiamide. N. Engl. J. Med., 309, 433-434.
8. Bruntsch U., Drechsier S., Hiller E., et al. (1992) : Prevention of chemotherapy-induced nausea and emesis in patients responding poorly to previous antiemetic therapy. Comparing tropisetron with optimised standard antiemetic therapy. Drugs, 43 (Suppl. 3): 23-26.
9. Fischer V., Baldeck J-P., Tse F. (1992) : Pharmacokinetics and metabolism of the 5-hydroxytryptamine antagonist tropisetron after single oral doses in humans. Drug Metab. Dispos., 20, 603-607.
10. De Bruijn K.M. (1992) : Tropisetron: a review of the clinical experience. Drugs, 43 (Suppl. 3): 11-22.
11. Fischer V., Vickers A.E.M., Heitz F., et al. (1994) : The polymorphic cytochrome P4502D6 is involved in the metabolism of both 5-hydroxytryptamine antagonists, tropisetron and ondansetron. Drug Metab. Dispos., 22, 269-274.
12. Firkusny L., Kroemer H.K., Eichelbaum M. (1995) : Characterization of cytochrome P-450 catalysed metabolism of the antiemetic tropisetron: a molecular base for interindividual variability and interaction potential. Biochem. Pharmacol., 49, 1777-1784.
13. Fischer V., Baldeck J.P., Wiebel F.J. (1987) : Metabolism of the tropine indole-3-carboxylate ICS 205-930 by differentiated rat and human hepatoma cells. Mo]. Toxicol., 1, 341-350.
14. Vickers A.E.M., Fischer V., Connors S. et al. (1992) : Cyclosporin A metabolism in human liver, kidney, and intestine slices. Comparison to rat and dog slices and human cell fines. Drug Metab. Dispos., 20, 802-809.
15. Vickers A.E.M., Connors S., Zollinger M. et al. (1993) : The biotransformation of the ergot derivative CQA 206-291 in human, dog, and rat liver slice cultures and prediction of in vivo plasma clearance. Drug Metab. Dispos., 21, 454-459.
16. Smith P.F., Krack G., McKee R.L. et al. (1986) : Maintenance of adult rat liver slices in dynamic organ culture. In vitro Cell Dev. Biol., 22, 706-712.
17. Connors S., Rankin D.R., Gandolfi A.J., Krumdieck C.L., Koep L.J., Brendel K. (1990) : Cocaine hepatotoxicity in cultured liver slices: a species comparison. Toxicology, 61, 171-183.
18. Bradford M. (1976) : A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem., 72, 248-254.
19. Dannan G.A., Guengerich F.P. (1982): Immunochemical comparison and quantitation of microsomal flavin-containing monooxygenases in various hog, mouse, rat, rabbit, dog, and human tissues. Mol. Pharmacol., 22, 787-794.