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fluoroquinolones, pharmacokinetics, pharmacodynamics, adverse effects

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Khaitovych, M. (2019). CLINICAL PHARMACOLOGY OF FLOROCHINOLONS: A FOCUS ON SAFETY. Review. Medical Science of Ukraine (MSU), 15(3-4), 90-97.


Fluoroquinolones are effective in the treatment of infections of almost any localization (upper and lower respiratory tract, urinary system, skin and soft tissues, bones and joints, liver and bile ducts, gastrointestinal tract, female genital tract, central nervous system, intra-abdominal), sexually transmitted infections. Resistance is slowly formed to fluoroquinolones. Among the benefits of certain fluoroquinolones are that they can be administered either orally or intravenously. Fluoroquinolones can also be combined with antibacterial agents of other groups. Levofloxacin (the left-turning isomer of ofloxacin) has now become one of the most commonly used antibiotics. This is because the drug exhibits high tissue penetration, creating in the alveolar macrophages, the mucous membranes of the bronchi and fluid lining the respiratory epithelium, a concentration that is significantly higher than the MIC to respiratory pathogens. The literature review presents current insights on the pharmacokinetics, pharmacodynamics, and adverse effects of fluoroquinolones. The risks of tendinitis, tendon ruptures, aortic aneurysm / dissection, QT prolongation, recurrence of C.difficile antibiotic-associated diarrhea, hypo- and hyperglycemic conditions are emphasized. The clinical role of fluoroquinolones inhibitory effect on cytochrome P450 isoenzymes CYP1A2 and CYP2C9 activities, which metabolize many drugs with low therapeutic index (derivatives of sulfonylureas, warfarin, phenytoin, and theophylline etc). Therefore, when deciding on the prescription of fluoroquinolones, especially for elderly patients, the doctor should collect a detailed anamnesis, in particular regarding the administration of drugs with a small therapeutic index, and conduct therapeutic drug monitoring, including monitoring blood glucose levels.
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1. Babushkina A.V. [Levofloxacin. Aspects of clinical use] // Ukrainian Medical Chronicle. 2010; 76 (2): 60-70. [in Russian] URL:
2. Zaytsev A.A., Sinopalnikov A.I. [“Respiratory” fluoroquinolones in the treatment of respiratory tract infections] // Russian Medical Journal. 2010; 30: 1886. [in Russian] URL:
3. [Fluoroquinolones: a place in clinical practice: reference book] / Ed.: Yu.M. Mostovoy, T.V. Konstantinovich. – Vinnitsa, 2009. 32 p. [in Russian]
4. Sidorenko S.V. Fluoroquinolones: Properties and Clinical Application // Difficult Patient. 2011; 9 (5): 21-7. [in Russian]. URL:
5. Fedorova O.A. [Moxifloxacin in the arsenal of combating multiresistant infections] // Ukrainian Medical Journal. 2014; 102 (4): 82-6. [in Russian]. URL:
6. Khaitovych M.V. Pharmacokinetic / pharmacodynamic model of antibiotic therapy: clinical application // Medical Science of Ukraine. 2017; 12 (3-4): 114-21. [in Ukrainian]. URL:
7. Aspinall S.L., Good C.B., Jiang R. Severe dysglycemia with the fluoroquinolones: a class effect? // Clin Infect Dis. 2009; 49 (3): 402-8.
8. Baillargeon J., Holmes H.M., Lin Y.L. et al. A new respiratory fluoroquinolone, oral gemifloxacin: a safety profile in context // Int J Antimicrob Agents. 2004; 23 (3): 421-9.
9. Bidell M.R., Lodise T.P. Fluoroquinolone-Associated Tendinopathy: Does Levofloxacin Pose the Greatest Risk? // Pharmacotherapy. 2016; 36 (6): 679-93.
10. Briones-Figueroa A., Sifuentes-Giraldo W.A., Morell-Hita J.L. et al. Achilles Tendon Rupture Associated with the Use of Fluoroquinolones in Patients Over 60 Years of AGE: Experience From a Single Tertiary Centre // Reumatol Clin. 2019. pii: S1699-258X(19)30125-1.
11. Chou H.W., Wang J.L., Chang C.H. et al. Risk of Severe Dysglycemia Among Diabetic Patients Receiving Levofloxacin, Ciprofloxacin, or Moxifloxacin in Taiwan / // Clin Infect Dis. 2013; 57 (7): 971-80.
12. Davis S.L., Neuhauser M.M., McKinnon. Quinolones // URL:
13. Dean L. Warfarin Therapy and VKORC1 and CYP Genotype / In: Medical Genetics Summaries [Internet]. Editors: Pratt V, McLeod H, Rubinstein W et al. / National Center for Biotechnology Information (US); 2012. URL:
14. Mays S. Drug-Drug Interaction Primer: A Compendium of Case Vignettes for the Practicing Clinician // Am J Psychiatry. 2008; 165 (3): 404.
15. Elbe D.H., Chang S.W. Moxifloxacin-warfarin interaction: a series of five case reports / // Ann Pharmacother. 2005; 39 (2): 361-4.
16. Elliot D.J., Suharjono S., Lewis B.C. et al. Identification of the human cytochromes P450 catalysing the rate-limiting pathways of gliclazide elimination // British Journal of Clinical Pharmacology. 2007; 64 (4): 450-7.
17. Etminan M., Sodhi M., Ganjizadeh-Zavareh S. et al. Oral Fluoroquinolones and Risk of Mitral and Aortic Regurgitation // J. Am. Coll. Cardiol. 2019; 74 (11): 1444-50.
18. Pham T.D.M., Ziora Z.M., Blaskovich M.A.T. Quinolone antibiotics // Med. Chem. Commun. 2019; 10: 1719-39. URL:!divAbstract
19. FDA reinforces safety information about serious low blood sugar levels and mental health side effects with fluoroquinolone antibiotics; requires label changes URL:
20. Haeseker M., Stolk L., Nieman F. et al. The ciprofloxacin target AUC: MIC ratio is not reached in hospitalized patients with the recommended dosing regimens // Br J Clin Pharmacol. 2013; 75 (1): 180-5.
21. Granados J., Ceballos M., Amariles P. Hypo or hyperglycemia associated with fluoroquinolone use // Rev Med Chil. 2018; 146 (5): 618-26.
22. Granfors M.T., Backman J.T., Neuvonen M., Neuvonen P.J. Ciprofloxacin greatly increases concentrations and hypotensive effect of tizanidine by inhibiting its cytochrome P450 1A2-mediated presystemic metabolism // Clin Pharmacol Ther. 2004; 76 (6): 598-606.
23. Grillon A., Schramm F., Kleinberg M., Jehl F. Comparative Activity of Ciprofloxacin, Levofloxacin and Moxifloxacin against Klebsiella pneumoniae, Pseudomonas aeruginosa and Stenotrophomonas maltophilia Assessed by Minimum Inhibitory Concentrations and Time-Kill Studies // PLoS One. 2016; 11 (6): e0156690.
24. Ismail M., Noor S., Harram U. et al. Potential drug-drug interactions in outpatient department of a tertiary care hospital in Pakistan: a cross-sectional study // BMC Health Serv Res. 2018; 18 (1): 762.
25. Ji Y., Hokayem H. Moxifloxacin-warfarin interaction // J Community Hosp Intern Med Perspect. 2011; 1 (4): Article: 11512
26. Karaoui W.R., Rustom L.B.O., Bou Daher H. et al. Incidence, outcome, and risk factors for recurrence of nosocomial Clostridioides difficile infection in adults: A prospective cohort study // J Infect Public Health. 2019. pii: S1876-0341(19)30343-0.
27. Lubasch A., Keller I., Borner K. et al. Comparative pharmacokinetics of ciprofloxacin, gatifloxacin, grepafloxacin, levofloxacin, trovafloxacin, and moxifloxacin after single oral administration in healthy volunteers // Antimicrob Agents Chemother. 2000; 44 (10): 2600-3.
28. Lane M.A., Zeringue A., McDonald J.R. Serious Bleeding Events due to Warfarin and Antibiotic Co-Prescription in a Cohort of Veterans // Am J Med. 2014; 127 (3): 657-63.
29. Lee C.C., Lee M.G., Hsieh R. et al. Oral Fluoroquinolone and the Risk of Aortic Dissection // J Am Coll Cardiol. 2018; 72 (12): 1369-78.
30. Liaqat A., Khan A.U., Asad M., Khalil A.H. Effect of Quinolones Versus Cefixime on International Normalized Ratio Levels After Valve Replacement Surgery with Warfarin Therapy // Medicina (Kaunas). 2019; 55 (10): pii: E644.
31. Meyer J.M., Proctor J., Cummings M.A. et al. Ciprofloxacin and Clozapine: A Potentially Fatal but Underappreciated Interaction // Case Rep Psychiatry. 2016; 2016 (3): 5606098.
32. Pakzad I., Zayyen Karin M., Taherikalani M. et al. Contribution of AcrAB efflux pump to ciprofloxacin resistance in Klebsiella pneumoniae isolated from burn patients // GMS Hyg Infect Control. 2013; 8 (2): Doc15.
33. Sharma P.C., Jain A., Jain S. et al. Ciprofloxacin: review on developments in synthetic, analytical, and medicinal aspects // Journal of Enzyme Inhibition and Medicinal Chemistry. 2010; 25 (4): 577-89.
34. Surendiran A., Pradhan S.C., Agrawal A. et al. Influence of CYP2C9 gene polymorphisms on response to glibenclamide in type 2 diabetes mellitus patients // Eur J Clin Pharmacol. 2011; 67 (8): 797-801.
35. Szałek E., Kamińska A., Gozdzik-Spychalska J. et al. The PK/PD index (CMAX/MIC) for ciprofloxacin in patients with cystic fibrosis // Acta Pol Pharm. 2011; 68 (5): 777-83.
36. Tan M.G., Worley B., Kim W.B. et al. Drug-Induced Intracranial Hypertension: A Systematic Review and Critical Assessment of Drug-Induced Causes // Am J Clin Dermatol. 2019.
37. Veličković-Radovanović R., Catić-Đorđević A., Dinić K. et al. Metronidazole- and levofloxacin-induced psychotic disorders in chronic kidney patient // Eur J Hosp Pharm. 2019; 26 (6): 347-9.
38. Wynn G.H., Oesterheld J.R., Cozza K.L., Armstrong S.C. Clinical Manual of Drug Interaction Principles for Medical Practice // American Psychiatric Pub. 2008. 608 P. ISBN 978-1-58562-296-2.
39. Zanel G.G., Noreddin A.M. Pharmacokinetics and pharmacodynamics of the new fluoroquinolones: focus on respiratory infections // Curr Opin Pharmacol. 2001; 1: 459-63.
40. Zhang L., Wei M.J., Zhao C.Y., Qi H.M. Determination of the inhibitory potential of 6 fluoroquinolones on CYP1A2 and CYP2C9 in human liver microsomes // Acta Pharmacol Sin. 2008; 29 (12): 1507-14.
41. Zinner S.H., Lubenko I.Y., Gilbert D. et al. Emergence of resistant Streptococcus pneumoniae in an in vitro dynamic model that simulates moxifloxacin
concentrations inside and outside the mutant selection window: related changes in susceptibility, resistance frequency and bacterial killing // J Antimicrob Chemother. 2003; 52 (4): 616-22.
42. Zusso M., Lunardi V., Franceschini D. et al. Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway // J Neuroinflammation. 2019; 16 (1):148.
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