Fluoroquinolones Reported Hepatotoxicity

Abstract

Fluoroquinolones are known to be safe and well tolerated. They are said to have the widest clinical acceptability when compared with other antibiotics. Their reported side effects include gastrointestinal tract, central nervous system effect and blood disorder. Rare side effects include phototoxicity, hypersensitivity, convulsion, psychosis, tendinitis, hypoglycemia, cardiotoxicity and nephrotoxicity. Some of these side effects have led to the withdrawal of some fluoroquinolones like travofloxacin from clinical use in some countries. Of recent fluoroquinolones induce cardiotoxicity and hepatotoxicity has gain attention. Due to increasing reports on fluoroquinolones associated hepatotoxicity in experimental Animal studies and clinical experience. This study reviews reported hepatotoxicity associated with clinically used fluoroquinolones and their safety profile on liver function. It was observed that some fluoroquinolones may have hepatotoxic potential. Reported fluoroquinolones induce hepatotoxicity manifested as hepatitis, pancreatis, jaundice, liver injury and hepatic failure. Most reported cases of fluoroquinolones induced hepatotoxicity were marked by elevated levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, direct bilirubin, total bilirubin and prolong prothrobin time. In some reported cases liver biopsy revealed hepatocellular damage, necrosis and degeneration. Mixed inflammatory infiltrates containing eosinophils, portal edema, bile ductular proliferation and lobular cholestasis were also observed in some cases. The mechanism of fluoroquinolones induce hepatotoxicity may involve generation of oxidative radicals in the liver during drug metabolism which induces DNA damage, mitochondrial damage and gene regulation leading to hepatocellular damage. This was observed in travofloxacin which enhances hepatic mitochondrial peroxynitrite stress in mice with underlying increased basal levels of super oxide leading to the disruption of critical mitochondrial enzyme and gene regulation. This mechanism could be associated with fluoroquinolones mechanism of action which includes DNA damage. In conclusion fluoroquinolones are well tolerated but some may have hepatotoxic potential. Most clinically used fluoroquinolones are relatively safe but Clinicians should consider patients liver function status before fluoroquinolones clinical recommendation. In some cases biochemical parameters associated with liver function should be monitored in patients with impaired liver function.

Share and Cite:

E. Adikwu and O. Deo, "Fluoroquinolones Reported Hepatotoxicity," Pharmacology & Pharmacy, Vol. 3 No. 3, 2012, pp. 328-336. doi: 10.4236/pp.2012.33044.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] C. M. Oliphant and G. M. Green, “Quinolones: A Comprehensive Review,” American Family Physician, Vol. 65, No. 3, 2002, pp. 455-464.
[2] P. B. Iannini, R. Kubin, C. Reiter and G. Tillotson, “Reassuring Safety Profile of Moxifloxacin,” Clinical Infectious Disease, Vol. 32, No. 1, 2001, pp. 1112-1114. doi:10.1086/319615
[3] A. J. Schaeffer, “The Expanding role of Fluoroquinolones,” American Journal of Medicine, Vol. 113, Suppl. 1A, 2002, pp. 45-54.
[4] H. Haixiao, L. Jun xiang, J. Yidun and L. Linguan, “Severe Liver Damage Caused by Levofloxacin,” Adverse Drug Reaction Journal, Vol. 1, 2009, p. 22.
[5] R. C. Owens and P. Ambrose, “Antimicrobial Safety: Focus on Fluo-roquinolones,” Clinical Infections Disease, Vol. 41, No. 51, 2005, pp. 44-57.
[6] European Agency for the Evaluation of Medicinal Products, “Public Statement on Travofloxacin Alatrofloxacin: Recommendation to Suspend the Marketing Authorization in the European Union,” London, 15 June 1999.
[7] M. K. Bhagirath, “A Case Report of Highly Suspected Ciprofloxacin-Induced Hepatotoxicity,” Turkey Journal of Gastroenterology, Vol. 9, No. 3, 2009, pp. 204-206.
[8] Direct Healthcare Professional Communication Regarding Moxifloxacin (Avelox?) and Serious Hepatic and Bullous Skin Reac-tions. Bayer HealthCare Medical Information Department, (Medicines and Healthcare Products Regulatory Agency (MHRA), Bayer). www.yeuowcard.gov.ukh
[9] N. E. Henann and M. F. Zambie, “Gatifloxacin-Associated Acute Hepatitis,” Pharmacotherapy, Vol. 21, No. 12, 2001, pp. 1579-1582. doi:10.1592/phco.21.20.1579.34479
[10] B. S. Thakur, A. I. Jain, S. Sirkar, G. Joshi, and R. Joshi, “Ciproflox-acin-Induced Cholestatic Jaundice,” Indian Journal of Gastroenterology, Vol. 26, 2007, pp. 51-52.
[11] A. Blum, “Ofloxacin-Induced Acute Severe Hepatitis,” Southern Medical Journal, Vol. 84, 1991, p. 1158. doi:10.1097/00007611-199109000-00027
[12] L. Xiao and C. Sheng, “Anaphylactic Shock with Liver Damage Caused by Levofloxacin Injection,” Chinese Journal of Drug Application and Monitoring, Vol. 7, No. 5, 2010, p. 32.
[13] FDA Issues Public Health Advisory on Liver Toxicity Associated with the Antibiotic Trovan [FDA Talk Paper], US Department of Health and Human Services, Food and Drug Administration, Rockville, 1999.
[14] D. N. Fish and D. S. North, “Gatifloxacin an Advanced 8-Methoxy Fluoroquinolone,” Pharmacotherapy, Vol. 21, No. 1, 2001, pp. 35-59. doi:10.1592/phco.21.1.35.34440
[15] T. Vial, M. Biour, J. Descotes and C. Trepo, “Antibiotics Associated Hepatitis Update from 1990,” Annals of Pharmacotherapy, Vol. 31, 1997, pp. 204-220.
[16] O. Cheung, K. Chopra, T. Yu and A. Obaid, “Gatifloxacin Induced Hepatotoxicity,” Annals of Internal Medicine, Vol. 140, 2004, pp. 72-73.
[17] C. I. Coleman, J. V. Spencer, J. O. Chung and P. Reddy, “Possible Gatifloxacin-Induced Fulminant Hepatic Failure,” Annals of Pharmacotherapy, Vol. 36, No. 78, 2002, pp. 1162-1167. doi:10.1345/aph.1A414
[18] K. Von Seggerm, R. Russo and M. A. Wikler, “A Novel Approach to Post Marketing Surveillance: The Tequin Clinical Experience Study [Abstr],” Program and Ab-stracts of the 40th Interscience Conference on Antimi-crobial Agents and Chemotherapy, American Society for Microbiology, Washington DC, 2000, p. 468.
[19] E. V. Caparelli, M. D. Reed, J. S. Bradley G L, Kearns, R. F. Jacobs, B. D. Damle, J. L. Blumer and D. M. Grasela, “Pharmacokinetics of Gatifloxacin in Infants and Children,” Antimicrobial Agents Chemotherapy, Vol. 49, No. 3, 2005, pp. 1106-1112. doi:10.1128/AAC.49.3.1106-1112.2005
[20] S. E. Or-man, H. S. Conjevaram, R. Vuppalachi, W. T. Freston, J. Rochen, E. D. Kleiner, P. H. Hayashi, “Clinical and His-topathologic Features of Fluoroquinolone-Induce Liver Injury,” Clinical Gastroenterology and Hepatology, Vol. 9, No. 6, 2011, pp. 517-523. doi:10.1016/j.cgh.2011.02.019
[21] A. Bogzil, G. Shams and S. Malhat, “Some Toxicological Heamatological and Biochemical Studies on Gatifloxacin in Rats,” Global Journal of pharmacology, Vol. 4, No. 3, 2001, pp. 151-153.
[22] H. Liu, “Safety Profile of the Fluoroqui-nolones: Focus on Levofloxacin,” Drug Safety, Vol. 33, No. 5, 2001, pp. 353-369. doi:10.2165/11536360-000000000-00000
[23] S. Coban, B. Ceydilek, F. Ekiz, E. Erden and L. Soykan, “Levof-loxacin-Induced Acute Fulminant Hepatic Failure in a Pa-tient with Chronic Hepatitis B Infection,” Annals of Pharmacotherapy, Vol. 39, 2005, pp. 1737-1740. doi:10.1345/aph.1G111
[24] F. Carrascosa, M. I. Lucena, R. J. Andrade, J. S. Caviedes, A. C. Lavin, J. C. Mones, A. P. Vicente, B. Serrano, V. B. Serrano, “Fatal Acute Hepatitis after Sequential Treatment with Levofloxacin, Doxycycline, and Naproxen in a Patient Presenting with Acute Mycoplasma Pneumonia Infection,” Clinical The-rapeutics Vol. 31 No. 5, 2009, pp. 1014-1019. doi:10.1016/j.clinthera.2009.05.012
[25] K. Airey and E. Koller, “Acute Hepatitis Associated with Levofloxacin in a Patient with Renal Insufficiency,” Canadian Medical Association Journal, Vol. 169, 2003, p. 8
[26] A. Karim, S. Ahmed, L. J. Rossoff, R. K. Siddiqui and H. N. Stein-berg, “Possible Levofloxacin-Induced Acute Hepatocel-lular Injury in a Patient with Chronic Obstructive Lung Disease,” Clinical Infectious Disease, Vol. 33, No. 20, 200,1 pp. 88-90.
[27] T. Papastavros, L. T. Dolovich, A. Holbrook, L. Whitehead and M. Loeb, “Adverse Events Associated with Pyrazinamide in the Treatment of Latent Multidrug Resistant Tuberculosis,” Canadian Medical Association Journal, Vol. 167, No. 2, 2002, pp. 131-136.
[28] J. D. Schwalm and C. H. Lee, “Acute Hepatitis Associated with Oral Levofloxacin Therapy in a Hemodialysis Patient,” Canadian Medical Association Journal, Vol. 168, 2003, pp. 847-848.
[29] L. Spahr, L. Rubbia Brandt, O. Marinescu, B. Armenian and A. Ha-dengue, “Acute Fatal Hepatitis Related to Levofloxacin,” Journal of Hepatology, Vol. 35, No. 3, 2001, pp. 8-9.
[30] D. Mennecier, C. Thiolet, C. Bredin, Potier, B. Vergeau and O. Farret, “Acute Pancreatitis after Treatment with Levofloxacin and Methylprednisolone,” Ga-stroenterologie Clinique Biologigue, Vol. 25, 2001, pp. 921-922.
[31] M. Hunt “Levofloxacin: Dysglycemia and Liver Disorders,” Canadian Adverse Reaction Newsletter, Vol. 17, No. 1. 2007, pp. 1-2. www.healthcanada.gc.ca/carn
[32] Levoquin (Levof-loxacin) Product Monogram, Jansen Inc, Toronto, Ontario, M3C IL9, Revised July 2011.
[33] J. B. Kahn, “Latest Industry Information on the Safety Profile of Levofloxacin in the US,” Chemotherapy, Vol. 47, Suppl. 3, 2001, pp. 32-37. doi:10.1159/000057842
[34] K. Yagawa, “Latest Industry Information on the Safety Profile of Levofloxacin in Japan,” Chemotherapy, Vol. 47, No. 3, 2001, pp. 38-43. doi:10.1159/000057843
[35] A. Koverech, M. Picari, F. Granata, R. Fostini, D. Toniolo and G. Recchia, “Safety Profile of Ofloxacin,” Italian Data Base Infection, Vol. 14, No. 4, 1986, pp. 335- 337.
[36] F. S. Jones and R. H. Smith, “Quinolones May Induce Hepatitis,” British Medical Journal, Vol. 314, 1997, p. 869. doi:10.1136/bmj.314.7084.869
[37] P. Gonzalez Carro, M. L. Huidobro, A. P. Zabala and E. M. Vicente, “Fatal Subfulminant Hepatic Failure with Ofloxacin,” American Journal of Gastroenterol, Vol. 95, No. 6, 2000, p. 1606. doi:10.1016/S0002-9270(00)00910-2
[38] M. Chaudhary, A. Tamta and R. Sehgal, “Sub-Chronic Toxicity Study of Fixed Dose Combination of Ofloxacin-Ornidazole in Musmusculus Mice,” The Open Toxicology Journal, Vol. 3, 2009, pp. 24-29.
[39] V. Onrust, M. Lamb, B. Barman and A. Julia. “Ofloxacin: A Reappraisal of Its Use in the Management of Genitourinary Tract Infections,” Drugs, Vol. 56, No. 5, 1998, pp. 895-928.
[40] M. I. Lucena, R. J. Andrade, H. S. Martinez, J. M. Perez- Serrano and A. Gomez-Outes, “Norfloxacin-Induced Eosinophilic Necro-tizing Granulomatous Hepatitis,” American Journal of Gastroenterology, Vol. 95, No. 12, 2000, p. 3662.
[41] M. Romero-Gomez, E. S. Garcia, and M. C. Fernandez, “Norfloxacin-Induced Acute Cholestatic He-patitis in a Patient with Alcoholic Liver Cirrhosis,” American Journal of Gastroenterology, Vol. 94, 1999, pp. 2324-2325. doi:10.1111/j.1572-0241.1999.02324.x
[42] M. I. Lucena, R. J. Andrade, H. S. Martinez, J. M. Perez-Serrano and A. Gomez-Outes, “Norfloxacin Induced Cholestatic Jaundice,” American Journal of Gastroenterology, Vol. 93, No. 2, 1998, p. 2309. doi:10.1111/j.1572-0241.1998.02309.x
[43] A. G. Gil-man, T. N. Rail, A. S. Nies and P. Taylor, “The Pharma-cological Basis of Therapeutics,” 8 Edition, Pergamon, New York, 1990, pp. 1057-1060.
[44] Y. J. Drabo, A. Niakara and H. Ouedraogo, “Acute Pancreatitis Secondary to Administration or Norfloxacin,” Annales Francasises d Anesthesie et de Reanimation, Vol. 21, 2002, pp. 68-69. doi:10.1016/S0750-7658(01)00562-7
[45] E. B. Bjomsson, R. Olsson and H. Remotti, “Norfloxacin- Induced Eosinophilic Necrotizing Granulomatous Hepatitis,” American Journal of Gastroenterology, Vol. 95, No. 12, 2000, p. 3662.
[46] A. Maura, A. Dino, A. Gardella, and C. Falugi, “Micronucleus Formation in Fetal Maternal Rat Erythroblasts after Norfloxacin Transplacental Administration,” Mutatio Research, Vol. 312, No. 2, 1994, pp. 127-130.
[47] Noroxin (Norfloxacin) Prescribing Information, K, MERCK and CO. INC White House Station, NJ.
[48] A. Torres, J. F. Muri, P. Corris, R. Kubin, I. Duprat-Lomon, P. P. Sagnier and G. Hoffken, “Effectiveness of Oral Moxifloxacin as Standard First Line Therapy in Community Acquired Pneumonia,” European respiratory Journal, Vol. 21, 2003, pp. 135-143. doi:10.1183/09031936.03.00045202
[49] R. Verma, R. Dhamija, D. Batts, S. C. Rossand and M. E. Loehrke, “Moxifloxacin Induced Fatal Hepatotoxicity in a 72-Year-Old Man: A Case Report,” Cases Journal, Vol. 2, 2009, pp. 1-3. doi:10.4076/1757-1626-2-8063
[50] S. Nori, C. Nebesio, R. Brasheav and J. B. Travers, “Moxif-loxacin Associated Drug Hypersensitivity Syndrome with Toxic Epidermal Necrolysis and Fulminant Hepatic Failure,” Archives of Dermatology, Vol. 104, 2004, pp. 1537-1538. doi:10.1001/archderm.140.12.1537
[51] S. Soto, L. Lopez-Roses, A. Avila Lancho, A. Gonzalez, E. Santos and B. Urraca, “Moxifloxacin-Induced Acute Liver Injury,” American Journal Gastroenterology, Vol. 97, 2002, pp.1853-1854. doi:10.1111/j.1572-0241.2002.05873.x
[52] Bayer Corporation, Avelox Safety Profile. http://www.avelox.com/Aveloxlavx_iv_safety.htm
[53] E. Von Kentz and G. Schluter, “Preclinical Safety Evaluation of Moxifloxacin a Novel Fluoroquinolone,” Journal of Antimicrobial Chemotherapy, Vol. 43, Suppl. B, 1999, pp. 91-100.
[54] P. B. Iannini, R. Kubin, C. Reiter and G. Tillotson, “Reassuring Safety Profile of Moxifloxacin,” Clinical Infectious Disease, Vol. 32, No. 1, 2001, pp. 1112-1114. doi:10.1086/319615
[55] C. Ho, Y. Chen, F. Hu, C. Yu, P. Yang and R. Lun, “Safety of Fluoroquinolone Use in Patients with Hepatotoxicity Induced by Anti-Tuberculosis Regimen,” Clinical Infections Disease, Vol. 48, 2009, pp. 1526-1533. doi:10.1086/598929
[56] P. Ball, L. Mandell, Y. Niki and G. Tillotson, “Comparative Tolerability of the Newer Fluoroquinolone Antibacterial,” Drug Safety, Vol. 2l, 2009, pp. 407-421.
[57] D. Hooper, “Quinolones,” In: G. L. Mandell, J. E. Bennett and R. Dolin, Eds., Mandell, Douglas, and Bennett’s Principles and Practice of Infectious Diseases, 5th Edition, Churchill Livingstone, Phila-delphia, 2000, pp. 404- 423.
[58] F. Pea, F. Pavan and E. Lugatti, “Pharmacokinetic and Pharmacokinetic and Pharmacodynamics Aspect of oral Moxifloxacin 400 mg 1 Day in Elderly Patients with Acute Exaorbation of Chronic Bronchitis,” Clinical Pharmacokinetics, Vol.45, 2006, pp. 287-295. doi:10.2165/00003088-200645030-00004
[59] A. Zimp-fer, A. Prospst, G. Mikuz, W. Vogel, L. Terracciano and S. Stadmann, “Ciprofloxacin Induced Acute Liver Injury: Case Report and Review of Literature,” Virchows Archive, Vol. 444, No. 1, 2004, pp. 87-89. doi:10.1007/s00428-003-0917-9
[60] J. K. Labowitz and W. B. Silverman, “Cholestatic Jaundice Induced by Ci-profloxacin,” Digestive Disease and Science, Vol. 42, 1997, pp. 192-194. doi:10.1023/A:1018870029216
[61] A. Aggarwal and J. Gurka, “Probable Ciprofloxacin Induced Cholestasis,” Australian New Zealand Journal Medicine, Vol. 25, No. 5, 1995, pp. 541-542. doi:10.1111/j.1445-5994.1995.tb01506.x
[62] J. P. Vil-leneuve, C. Davies and J. Cole, “Suspected Ciproflox-acin-Induced Hepatotoxicity,” Annals of Pharmacotherapy, Vol. 29, 1995, pp. 294-296.
[63] A. C. Hirsch and L. M. Lundquist, “Ciprofloxacin-Induce Hepatotoxicity Resolved with Levofloxacin: A Case Report and a Review of the Literature,” Hospital Pharmacy, Vol. 44, No. 11, 2009, pp. 978-983. doi:10.1310/hpj4411-978
[64] A. J. Dichiara, Alkinson, Z. Goodman and H. E. Sherman, “Ciprofloxacin-Induced Acute Cholestatic Liver Injury and Associated Renal Failure Case Report and Review,” Minerva Gastroente-rologica e Dietologica, Vol. 54, No. 3, 2008, pp. 307-315.
[65] Z. M. Goetz, P. R. Galle and A. Schwart-ing, “Non Fatal Acute Liver Injury Possibly Related to High-Dose Ciprofloxacin,” European Journal of Clinical Microbiology and Infectious Disease, Vol. 22, No. 5, 2003, pp. 294- 296.
[66] M. Alcalde, M. S. Donoso, M. Carda Diaz and J. M. Puscosio Narvaezi, “Liver Dysfunction Due to Ciprofloxacin,” Acta Gastroenterologica Belgica, Vol. 58, No. 5, 1995, pp. 475-476.
[67] O. Sherman and J. L. Beizer, “Possible Ciprofloxacin— Induce Acute Cholestatic Jaundice,” Annals of Pharmacotherapy, Vol. 28, No. 10, 1994, pp. 1162-1164.
[68] E. Cholongitas, C. Georgousaki, S. Spyrou and M. Deisenaki, “Ciprofloxacin Induce Acute Cholestatic Hepatic Jaundice,” Annals of Hepatology, Vol. 83, No. 4, 2001, pp. 400-401.
[69] M. Pfeiffer, C. Reiter, S. Fuchs and M. Simonz, “Fatal Hepatic Failure Associated with Ciprofloxacin,” Lancet, Vol. 343, No. 8899, 1994, pp. 738-739. doi:10.1016/S0140-6736(94)91624-1
[70] B. K. Grass-mick, V. T. Lehr and A. S. Sundareson, “Fulminant He-patic Failure Possibly Related to Ciprofloxacin,” Annals of Pharmacotherapy, Vol. 26, No. 5, 1992, pp. 636-639.
[71] S. A. Zaidi, “Hepatitis Associated with Amoxicillin/ Clavulanic Acid and/or Ciprofloxacin,” American Journal of Medical Sciences, Vol. 325, 2003, pp. 31-33. doi:10.1097/00000441-200301000-00006
[72] S. Fuchs, Z. Simeon and M. Brezis, “Fatal Hepatic Failure Asso-ciated with Ciprofloxacin,” Lancet, Vol. 19, No. 343, 1994, pp. 738-739. doi:10.1016/S0140-6736(94)91624-1
[73] J. R. Levinson and A. Kumar, “Ciprofloxacin-Induced Cholestatic Jaun-dice: A Case Report (Abstract),” American Journal of Gastroenterology, Vol. 88, 1993, p. 1619.
[74] M. A. Channa and M. Z. Janjua, “Effects of Ciprofloxacin on Fetal Hepatocytes,” Journal of Pakistan Medical Association, Vol. 53, No. 10, 2003, pp. 448-450.
[75] G. Y. Minuk, N. Assy and L. X Ding, “Effects of Quinolone Antibiotic on Hepatic Growth and Protein Synthesis Following Partial Hepatectomy in Rats,” Journal of Gastro-enterology and Hepatology, Vol. 12, 1997, pp. 5-7. doi:10.1111/j.1440-1746.1997.tb00346.x
[76] A. Basaran, K. Erol, N. Basaran, H. V. Gunes, E. Acikalin, P.G. Timural, I. Degirmenci, E. A. Cakmak and A. G. Tomati, “Effect of Ciprofloxacin on Chromosomes, and Hepatic and Renal Functions in Rats,” Chemotherapy, Vol. 39, No. 3, 1993, pp. 182-188. doi:10.1159/000239124
[77] H. I. Nadia, “Assessment of Histopathological and Histological Changes in Liver of Pregnant Female Rats then Fetuses Following Ciproflox-acin Administration,” Journal of Egypt society of Toxicology, Vol. 35, 2006, pp. 7- 17.
[78] A. I. Weyers, U. I. Laura, G. O. Hugo and B. G. Nora, “Ciprofloxacin In-creases Hepatic and Renal Lipid Hydroperoxide Levels in Mice,” Biocell, Vol. 26, No. 2, 2002, pp. 225-228.
[79] G. Y. Minuk, T. Gauthier, X. K. Zhang, G. Q. Wang and F. T. Burczynski, “Ciprofloxacin Reverses the Inhibitory Effects of Acute Ethanol Exposure on He-patic Regeneration in the Rat,” Hepatology, Vol. 22, 1995, pp. 1797- 1800.
[80] R. Stahlmann, “Clinical Toxico-logical Aspects of Fluoroquinolones,” Toxicology Letters, Vol. 127, 2002, pp. 269- 277. doi:10.1016/S0378-4274(01)00509-4
[81] H. J. Chen, K. J. Bloch and J. A. Maclean, “Acute Eosinophilic Hepatitis from Travofloxacin,” New England Journal of Medicine, Vol. 42, No. 5, 2000, pp. 359-360. doi:10.1056/NEJM200002033420517
[82] D. A. La-zarczyk, N. S. Goldstein and S. C. Gordon, “Abstract Travofloxacin Hepatotoxicity,” Digestive Disease and Sciences, Vol.46, No. 4, 2001, pp. 925-926. doi:10.1023/A:1010741510046
[83] K. H. Pannu, L. Gohlieb and K. E. Fishman, “Acute Liver Failure Due to Travofloxacin; CT Findings,” Emergency Radiology, Vol. 8, 2001, pp. 108-110. doi:10.1007/PL00011876
[84] J. Borlak, “Travofloxacin: A Case Study of Idiosyncratic or Iatrogenic Liver Toxicity-Molecular Mechanism and Lessons for Pharmacotoxicity,” Human and Experimental Toxicology, Vol. 28, 2004, pp. 119-121. doi:10.1177/0960327109105767
[85] M. I. Lucena, R. J. Andrade, L. Rodrigo, J. Salmeron, A. Alvarez, M. J. Lopez-Garrido, R. Camargo and R. Acantara, “Travofloxacin Induced Acute Hepatitis,” Clinical Infectious Disease, Vol. 30, No. 2, 2000, pp. 400-401. doi:10.1086/313680
[86] M. J. Liguori, M. G. Anderson, S. Bukofzer, J. McKim and J. F. Waring, “Suggested Mechanism for Hepatotoxicity Induced by Travofloxacin,” Hepatology, Vol. 4, No. l, 2005, pp. 177-186. doi:10.1002/hep.20514
[87] FDA Medical Officer’s Safety Update (April 1998 to June 1998), pp. 5-6.
[88] FDA Pharmacology Review, 18 December 1997.
[89] Trovanproject Monogram Produced by Pfizer Inc., 1998, Reviewed July 1998.
[90] Travofloxacin/Alatrofloxacin, Pharmacology Review, 1997, pp. 43-44.
[91] J. F. Waring, M. J. Liguori, J. P. Luyendyk, J. F. Maddox, P. E. Ganey, R. F. Stachlewitz, C. North, E. A. Blomme and R. A. Roth, “Microarray Analysis of Lipopolysaccharide Potentiation of Travofloxacin Induced Liver Injury in Rats Suggests a Role for Proinflammatory Chemokines and Neutrophils,” Journal of Pharmacology and Experimental Therapeutics, Vol. 316, No. 3, 2006, pp. 1080- 1087. doi:10.1124/jpet.105.096347
[92] P. J. Shaw, M. I. Hop-fensperger, P. E. Ganey and R. A. Roth, “Lipopolysac-charide and Travofloxacin Coexposure in Mice Causes Idiosyncrasy Like Liver Injury Dependent on Tumor Ne-crosis Factor-Alpha,” Toxicological Sciences, Vol. 100, No. 1, 2007, pp. 259-266. doi:10.1093/toxsci/kfm218
[93] Travofloxacin/Alatrofloxacin, Pharmacology Review, 18 December 1997, p. 42.
[94] Public Statement on Trovan/Trovan IV/Turvel/Turvel IV (Travofloxacin/Alatrofloxacin) [Press Release 15770/99]. European Agency for the Evaluation of Medicinal Products, London, 25 May 1999.
[95] G. Labbe, D. Pessayre and B. Fromenty, “Drug Induced Liver Injury through Mitochondria Dysfunction; Mechanisms and Detection during Preclinical Safety Studies,” Fundamental and Clinical Pharmacology, Vol. 22, 2008, pp. 335-353. doi:10.1111/j.1472-8206.2008.00608.x
[96] M. P. Holt and C. Ju, “Mechanism of Drug Induced Liver Injury,” American Association of Pharmaceutical Scientists Journal, Vol. 8, No. 1, 2006, pp. 48-54.
[97] C. J. Hsiao, H. Younis and U. A. Boelsterli, “Travofloxacin, a Fluo-roquinolone Antibiotic with Hepatotoxic Potential, Causes Mitochondrial Peroxynitrite Stress in a Mouse Model of Underlying Mitochondrial Dysfunction,” Chemico-Biological Interactions, Vol. 188, No. 1, 2010, pp. 204-213. doi:10.1016/j.cbi.2010.07.017
[98] Q. Sun, R. Zhu, F. W. Foss and T. L. Macdonald, “In Vitro Metabolism of a Model Cyclopropylamine to Reactive Intermediate: Insights into Travofloxacin-Induced Hepatotoxicity,” Chemical Research in Toxicology, Vol. 21, No. 3, 2008, pp. 711-719. doi:10.1021/tx7003085
[99] P, Jones, J. Lemasters, D. Han, A. U. Boelsterli and N. Kaplowitz, “Mechanisms of Pathogenesis in Drug Hepatotoxicity, Putting the Stress on Mitochondria,” Molecular Interventions, Vol. 10, No. 2, 2010, pp. 98-111. doi:10.1124/mi.10.2.7
[100] A. A. Pino, A. V. Maura and L. Masciangelo, “Evaluation of DNA Damage Induced by Norfloxacin in Liver and Kidney of Adult Rats and Fetal Tissues after Transplacental Exposure,” Mutation Research, Vol. 264, 1991, pp. 81-85. doi:10.1016/0165-7992(91)90049-A
[101] Y. Kashida, Y. Sasaki, K. Oshawa, N. Yokohama, A. Takahashi, T. Wa-tanabe and K. Mitsumori, “Mechanistic Study on Flumequine Hepatocarcinogenicity Focusing on DNA Damage in Mice,” Toxicological Science, Vol. 69, No. 2, 2002, pp. 317-321. doi:10.1093/toxsci/69.2.317
[102] F. Hincal and T. Taskin, “The Mechanism Induced by Ciprofloxacin May Involve the Generation of Free Radicals and the Activation of Excitatory Amino Acid Receptors,” Abstracts of the International Congress of Toxicology—VII Seattle, W.A. Abstr, No. 99, 1995, p. 27.

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.