In-vitro stability and metabolism of a tacrine-silibinin codrug

Journal of Pharmacy and Pharmacology

Volumn 65, Issue 12, 2013, Pages 1765-1772

  Zenger, Katharina ^a   Chen, Xinyu ^a,b   Decker, Michael ^a   Kraus, Birgit ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b UNIVERSITY OF WÜRZBURG   (Germany)

Author keywords

codrug; microsomal metabolites; silibinin; stability; tacrine

Indexed keywords

DRUG METABOLITE; MICROSOME ENZYME; SILIBININ; SILIBININ PLUS TACRINE; TACRINE; TACRINE HEMISUCCINAMIDE; UNCLASSIFIED DRUG;

ARTICLE; CELL VIABILITY; CHEMICAL BOND; CONTROLLED STUDY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DRUG DEGRADATION; DRUG GLUCURONIDATION; DRUG METABOLISM; DRUG STABILITY; DRUG STRUCTURE; ELECTROSPRAY MASS SPECTROMETRY; ESTER BOND; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INCUBATION TIME; LIQUID CHROMATOGRAPHY; LIVER MICROSOME; MITOCHONDRION; STELLATE CELL;

CODRUG; MICROSOMAL METABOLITES; SILIBININ; STABILITY; TACRINE;

CELL SURVIVAL; CELLS, CULTURED; CULTURE MEDIA; DRUG COMBINATIONS; DRUG STABILITY; HUMANS; MICROSOMES, LIVER; MITOCHONDRIA; SILYMARIN; TACRINE;

EID: 84887860861     PISSN: 00223573     EISSN: 20427158     Source Type: Journal    
DOI: 10.1111/jphp.12070     Document Type: Article

References (28)

1. Ballard C, et al. Alzheimer's disease. Lancet 2011; 377: 1019-1031.
2. Blackard WG, et al. Tacrine. A cause of fatal hepatotoxicity? J Clin Gastroenterol 1998; 26: 57-59.
3. Knapp MJ, et al. A 30-week randomized controlled trial of high-dose tacrine in patients with Alzheimer's disease. The tacrine study group. JAMA 1994; 271: 985-991.
4. Watkins PB, et al. Hepatotoxic effects of tacrine administration in patients with Alzheimer's disease. JAMA 1994; 271: 992-998.
5. Gracon SI, et al. Safety of tacrine: clinical trials, treatment IND, and postmarketing experience. Alzheimer Dis Assoc Disord 1998; 12: 93-101.
6. Fang L, et al. Design and synthesis of tacrine-ferulic acid hybrids as multi-potent anti-Alzheimer drug candidates. Bioorg Med Chem Lett 2008; 18: 2905-2909.
7. Lupp A, et al. Tacrine-NO donor and tacrine-ferulic acid hybrid molecules as new anti-Alzheimer agents: hepatotoxicity and influence on the cytochrome P450 system in comparison to tacrine. Arzneimittelforschung 2010; 60: 229-237.
8. Lange JHM, et al. Design, synthesis, biological properties, and molecular modeling investigations of novel tacrine derivatives with a combination of acetylcholinesterase inhibition and cannabinoid CB1 receptor antagonism. J Med Chem 2010; 53: 1338-1346.
9. Fang L, et al. Hybrid molecules from xanomeline and tacrine: enhanced tacrine actions on cholinesterases and muscarinic M1 receptors. J Med Chem 2010; 53: 2094-2103.
10. Chen X, et al. Tacrine-silibinin codrug shows neuro- and hepatoprotective effects in vitro and pro-cognitive and hepatoprotective effects in vivo. J Med Chem 2012; 55: 5231-5242.
11. Madden S, et al. Clinical pharmacokinetics of tacrine. Clin Pharmacokinet 1995; 28: 449-457.
12. Wu JW, et al. Drug-drug interactions of silymarin on the perspective of pharmacokinetics. J Ethnopharmacol 2009; 121: 185-193.
13. Spaldin V, et al. The effect of enzyme inhibition on the metabolism and activation of tacrine by human liver microsomes. Br J Clin Pharmacol 1994; 38: 15-22.
14. Madden S, et al. Species variation in the bioactivation of tacrine by hepatic microsomes. Xenobiotica 1995; 25: 103-116.
15. Becquemont L, et al. Influence of fluvoxamine on tacrine metabolism in vitro: potential implication for the hepatotoxicity in vivo. Fundam Clin Pharmacol 1996; 10: 156-157.
16. Larsen JT, et al. Fluvoxamine is a potent inhibitor of tacrine metabolism in vivo. Eur J Clin Pharmacol 1999; 55: 375-382.
17. Han YH, et al. Stereoselective metabolism of silybin diastereoisomers in the glucuronidation process. J Pharm Biomed Anal 2004; 3: 1071-1078.
18. Woolf T, et al. Liver reactions to tacrine. Handb Exp Pharmacol 1996; 121: 395-410.
19. Benoit GG, et al. Noninterference of cytochrome P4501A2 in the cytotoxicity of tacrine using genetically engineered V79 Chinese hamster cells for stable expression of the human or rat isoform and two human hepatocyte cell lines. Biochem Pharmacol 1997; 53: 423-427.
20. Meng Q, et al. Re-evaluation of tacrine hepatotoxicity using gel entrapped hepatocytes. Toxicol Lett 2007; 168: 140-147.
21. Schnabl B, et al. Immortal activated human hepatic stellate cells generated by ectopic telomerase expression. Lab Invest 2002; 82: 323-333.
22. Monteith DK, et al. Functional and subcellular organelle changes in isolated rat and human hepatocytes induced by tetrahydroaminoacridine. Arch Toxicol 1998; 72: 147-156.
23. Osseni RA, et al. Tacrine-induced reactive oxygen species in a human liver cell line: the role of anethole dithiolethione as a scavenger. Toxicol In Vitro 1999; 13: 683-688.
24. Lemasters JJ, et al. Mitochondrial dysfunction in the pathogenesis of necrotic and apoptotic cell death. J Bioenerg Biomembr 1999; 31: 305-319.
25. Berson A, et al. Uncoupling of rat and human mitochondria: a possible explanation for tacrine-induced liver dysfunction. Gastroenterology 1996; 110: 1878-1890.
26. Robertson DG, et al. Elucidation of mitochondrial effects by tetrahydroaminoacridine (tacrine) in rat, dog, monkey and human hepatic parenchymal cells. Arch Toxicol 1998; 72: 362-371.
27. Melo T, et al. Tacrine and its analogues impair mitochondrial function and bioenergetics: a lipidomic analysis in rat brain. J Neurochem 2012; 120: 998-1013.
28. Rasola A, Bernardi P,. The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis. Apoptosis 2007; 12: 815-833.