Inhibition of hepatobiliary transport as a predictive method for clinical hepatotoxicity of nefazodone

Toxicological Sciences

Volumn 90, Issue 2, 2006, Pages 451-459

  Kostrubsky, Seva E ^a   Strom, Stephen C ^a   Kalgutkar, Amit S ^b   Kulkarni, Shaila ^a   Atherton, James ^a   Mireles, Rouchelle ^b   Feng, Bo ^b   Kubik, Raylene ^a   Hanson, Janean ^a   Urda, Ellen ^a   Mutlib, Abdul E ^a  

^a PFIZER INC   (United States)

^b University of Pittsburgh Medical Center ^*

Author keywords

BSEP; Buspirone; Hepatocytes; Metabolism; Trazodone

Indexed keywords

1 AMINOBENZOTRIAZOLE; BILE ACID; BILE SALT; BUSPIRONE; GLUCURONIDE; NEFAZODONE; SULFATE; TRAZODONE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BILE ACID BLOOD LEVEL; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORRELATION ANALYSIS; CYTOTOXICITY; DRUG METABOLISM; DRUG STRUCTURE; GLUTATHIONE METABOLISM; HEPATOBILIARY SYSTEM; HUMAN; HUMAN CELL; IC 50; INCUBATION TIME; LIVER CELL; LIVER MICROSOME; LIVER TOXICITY; NONHUMAN; PREDICTION; PROTEIN SYNTHESIS INHIBITION; RAT;

ANIMALS; ANTIDEPRESSIVE AGENTS, SECOND-GENERATION; BILE ACIDS AND SALTS; BILE CANALICULI; BIOLOGICAL TRANSPORT; BUSPIRONE; CELLS, CULTURED; HEPATOCYTES; HUMANS; MICROSOMES, LIVER; RATS; RATS, SPRAGUE-DAWLEY; TRAZODONE; TRIAZOLES;

ANIMALIA;

EID: 33645114867     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfj095     Document Type: Article

References (28)

1. Aranda-Michel, J., Koehler, A., Bejarano, P. A., Poulos, J. E., Luxon, B. A., Khan, C. M., and Ee, L. C. (1999). Nefazodone-induced liver failure: Report of three cases. Ann. Intern. Med. 130, 285-288.
2. 14C]nefazodone in humans. Drug Metab. Dispos. 24, 91-95.
3. Barbhaiya, R., Marathe, P., Greene, D., Mayol, R., Shukla, U., Gammans, R., and Pittman, K. (1995). Safety, tolerance, and preliminary pharmacokinetics of nefazodone after administration of single and multiple oral doses to healthy adult male volunteers: A double-blind, Phase I study. J. Clin. Pharmacol. 35, 974-984.
4. Conway, C., McGuire, M. J., and Baram, V. (2004). Nefazodone-induced liver failure. Clin. Phychopharmacol. 24, 353-354.
5. Dockens, R., Greene, D., and Barbhaiya, R. (1996). Assessment of pharmacokinetic and pharmacodinamic drug interactions between nefazodone and digoxin in healphy male volunteers. J. Clin. Pharmacol. 36, 160-167.
6. Fattinger, K., Funk, C., Pantze, M., Weber, C., Reichen, J., Stieger, B., and Meier, P. (2001). The endothelin antagonist bosentan inhibits the canalicular bile salt export pump: A potential mechanism for hepatic adverse reactions. Clin. Pharmacol. Ther. 69, 223-231.
7. Funk, C., Ponelle, C., Scheuermann, G., and Pantze, M. (2001). Cholestatic potential of troglitazone as a possible factor contributing to troglitazone-induced hepatotoxicity: In vivo and in vitro interaction at the canalicular bile salt export pumb (Bsep) in the rat. Mol. Pharmacol. 59, 627-635.
8. Garcia-Pando, A. C., Poso, J. G., Sanchez, A. S., Martin, A. V., Castro, A. M., and Lucena, I. (2002). Hepatotoxicity associated with new antidepressants. J. Clin. Psychiatry 63, 135-137.
9. Harrel, A. W., Wheeler, S. M., East, P., Clarke, S. E., and Chenery, R. J. (1994). Use of rat and human in vitro systems to assess the effectiveness and enzymology of deoxyguanine analogs as prodrugs of an antiviral agent. Drug Metab. Dispos. 22, 189-193.
10. Ishizuka, I., Konno, K., Shiina, T., Naganuma, H., Nishimura, K., Ito, K., Suzuki, H., and Sugiyama, Y. (1999). Species differences in the transport activity for organic anions across the bile canalicular membrane. J. Pharmacol. Exp. Ther. 290, 1324-1330.
11. Kalgutkar, A. S., Vaz, A., Lame, M. E., Henne, K. R., Soglia, J., Zhao, S. X., Abramov, Y. A., Lombardo, F., Collin, C., Hendsch, Z. C., et al. (2005). Bioactivation of the nontricyclic antidepressant nefazodone to a reactive quinone-imine species in human liver microsomes and recombinant cytochrome P4503A. Drug Metab. Dispos. 33, 243-253.
12. Klaassen, C. D. (1973). Comparison of the toxicity of chemicals in newborn rats to bile duct-ligated and sham-operated rats and mice. Toxicol. Appl. Pharmacol. 24, 37-44.
13. Kostrubsky, V. E., Lewis, L. D., Wood, S. G., Sinclair, P. R., Wrighton, S. A., and Sinclair, J. F. (1997). Effect of taxol on cytochrome P4503A and acetaminophen toxicity in cultured rat hepatocytes: Comparison to dexamethsone Toxicol. Appl. Pharmacol. 142, 79-86.
14. Kostrubsky, V. E., Ramachandran, V., Venkataramanan, R., Dorrko, K., Esplen, J., Zhang, S., Sincalir, J. F., Wrighton, S., and Strom, S. C. (1999). The use of human hepatocytes cultures to study the induction of cytochrome P-450. Drug Metab. Dispos. 27, 887-894.
15. Kostrubsky, V. E., Sinclair, J. F., Ramachandran, V., Venkataramana, R., Wen, Y., Kindt, E., and Galchev., V. (2000). The role of conjugation on hepatotoxicity of troglitazone in human and porcine hepatocyte cultures. Drug Metab. Dispos. 28, 1192-1197.
16. Kostrubsky, V. E., Sinclair, J. F., Strom, S. C., Wood, S., Urda, E., Wen, Y. H., Kulkarni, S., and Mutlib, A. (2005). Phenobarbital and phenytoin induced acetaminophen hepatotoxicity due to inhibition of UDP-glucuronosyltransferases in cultured human hepatocytes. Toxicol. Sci. 87, 146-155.
17. Kostrubsky, V. E., Strom, S. C., Hanson, J., Urda, E., Rose, K., Burliegh, J., Zocharski, P., Sinclai, J. F., and Sahi, J. (2003). Evaluation of cholestatic potential of drugs by inhibition of bile acid transport in cultured primary human hepatocytes and intact rats. Predictability of drug-induced cholestatis. Toxicol. Sci. 76, 220-228.
18. Kostrubsky, V. E., Vore, M., Kindt, E., Burliegh, J., Rogers, K., Peter, G., Altrogge, D., and Sinz, M. (2001). The effect of troglitazone biliary excretion on metabolite distribution and cholestasis in transporter-deficient rats. Drug Metab. Dispos. 29, 1561-1566.
19. Lucena, M. I., Andrade, R. J., Gomez-outes, A., Rubio, M., and Cabello, M. R. (1999). Acute liver failure after treatment with nefazodone. Dig. Dis. Sci. 44, 2577-2579.
20. Mayol, R. F., Cole, C. A., Luke, G. M., Colson, K. L., and Kerns, E. H. (1994). Characterization of the metabolites of the antidepressant drug nefazodone in human urine and plasma. Drug Metab. Dispos. 22, 304-311.
21. NDA (2001). Hepatotoxicity boxed warning. New Drug Application (NDA) 20-152/S-028, supplemental application S-128, 12/4/2001.
22. Olson, H., Betton, G., Robinson, D., Thomas, K., Monro, A., Kolja, G., Lilly, P., Sanders, J., Sipes, G., Bracken, W., et al. (2000). Concordance of the toxicity of pharmaceuticals in humans and in animals. Regul. Toxicol. 32, 56-57.
23. Salazar, D., Frackiewicz, E., Dockens, R., Kollia, G., Fulmor, E., Tigel, P., and Uderman, H. (2001). Pharmacokinetics and tolerability of buspirone during oral administration to children and adolescents with anxiety disorder and normal healthy adults. J. Clin. Pharmacol. 41, 1351-1358.
24. 14C]nefazodone in the dogs. Drug Metab. Dispos. 21, 502-507.
25. Spigset, O., Hagg, S., and Bate, A. (2003). Hepatic injury and pancreatitis during treatment with serotonin reuptake inhibitors: Data from the World Health Organization (WHO) database of adverse drug reactions. Clin. Phychoparmacol. 18, 157-161.
26. Strom, S. C., Dorko, K., Thompson, M. T., Schuetz, J. D., and Schutz, E. G. (1996). Use of human hepatocytes to study P450 gene induction. Methods Enzymol. 272, 388-401.
27. Tzimas, G. N., Dion, B., and Deschenes, M. (2003). Early onset, nefazodone-induced fulminant hepatic failure. Am. J. Gastroenterol. 98, 1664.
28. Wen, Y. H., Sahi, J., Urda, E., Kulkarni, S., Rose, K., Zheng, X., Sinclair, J. F., Cai, H., Strom, S. C., and Kostrubsky, V. E. (2002). Effects of bergamottin on human and monkey drug-metabolizing enzymes in primary cultured hepatocytes. Drug Metab. Dispos. 30, 977-984.