Research Article | Open Access
Iman Y. Zaghloul, Yosef A. Asiri, Lamya S. Alnaim, Badraddin M. Al-Hadiya, "Co-administration of Fluoxetine Alters the Steady State Pharmacokinetics of Fluconazole after Multiple Oral Administration in Dogs", Scholarly Research Exchange, vol. 2009, Article ID 834879, 7 pages, 2009. https://doi.org/10.3814/2009/834879
Co-administration of Fluoxetine Alters the Steady State Pharmacokinetics of Fluconazole after Multiple Oral Administration in Dogs
Objectives. Fluconazole is an antifungal agent which has become the mainstay treatment of opportunistic fungal infections in immuno-compromized patients. Fluoxetine is a selective serotonine reuptake inhibitor used in the treatment of psychiatric disorders. In the current study we investigated the effect of chronic administration of fluoxetine on the steady state pharmacokinetics parameters of fluconazole. Methods. The pharmacokinetics of Fluconazole, following 10 mg/kg single and multiple oral dosing for 10 days, was determined in dogs. Subsequently, the effect of 2 mg/kg fluoxetine given for 10 days, on the pharmacokinetics of Fluconazole was investigated. Results. The co-administration resulted in significant reduction of 40.1% and 35.6% in , and , respectively compared to fluconazole alone. A significant alteration of was also seen as it increased from 0.242 0.04 to 0.654 0.17 l/kg (). Accordingly, a significant reduction in from 0.048 0.01 hr-1 to 0.031 0.01 was detected (). Conclusion. fluoxetine reduced plasma concentration of fluconazole. The mechanism of the interaction is probably the inhibition of OATP or other transporters in the intestinal wall. This interaction may have significant clinical importance because reduction in fluconazole may lead to treatment failure of fungal infection.
- T. Shimada, H. Yamazaki, M. Mimura, Y. Inui, and F. P. Guengerich, “Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians,” Journal of Pharmacology and Experimental Therapeutics, vol. 270, no. 1, pp. 414–423, 1994.
- M. T. Pasko, S. C. Piscitelli, and A. D. Van Slooten, “Fluconazole: a new triazole antifungal agent,” DICP, vol. 24, no. 9, pp. 860–867, 1990.
- R. L. Slaughter and D. J. Edwards, “Recent advances: the Cytochrome P450 enzymes,” Annals of Pharmacotherapy, vol. 29, no. 6, pp. 619–624, 1995.
- K. Richardson, “The discovery and profile of fluconazole,” Journal of Chemotherapy, vol. 2, no. 1, pp. 51–54, 1990.
- P. Benfield, R. C. Heel, and S. P. Lewis, “Fluoxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in depressive illness,” Drugs, vol. 32, no. 6, pp. 481–508, 1986.
- S. H. Preskorn, R. Shah, M. Neff, A. L. Golbeck, and J. Choi, “The potential for clinically significant drug-drug interactions involving the CYP 2D6 system: effects with fluoxetine and paroxetine versus sertraline,” Journal of Psychiatric Practice, vol. 13, no. 1, pp. 5–12, 2007.
- R. M. Lane, “Pharmacokinetic drug interaction potential of selective serotonin reuptake inhibitors,” International Clinical Psychopharmacology, vol. 12, no. 2, p. 126, 1997.
- J. F. Wernicke, “Safety and side effect profile of fluoxetine,” Expert Opinion on Drug Safety, vol. 3, no. 5, pp. 495–504, 2004.
- J. Amchin, L. Ereshefsky, W. Zarycranski, K. Taylor, D. Albano, and P. M. Klockowski, “Effect of venlafaxine versus fluoxetine on metabolism of dextromethorphan, a CYP2D6 probe,” Journal of Clinical Pharmacology, vol. 41, no. 4, pp. 443–451, 2001.
- S. M. Grant and S. P. Clissold, “Fluconazole: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in superficial and systemic mycoses,” Drugs, vol. 39, no. 6, pp. 877–916, 1990.
- P. O. Gubbins, S. A. McConnell, and S. R. Penzak, “Antifungal Agents,” in Drug Interactions in Infectious Diseases, S. C. Piscitelli and K. A. Rodvold, Eds., Humana Press, Totowa, NJ, USA, 2001.
- L. L. Von Moltke, D. J. Greenblatt, J. Schmider et al., “Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine, norfluoxetine, and by azole antifungal agents,” Journal of Clinical Pharmacology, vol. 36, no. 9, pp. 783–791, 1996.
- T. A. Ketter, D. A. Flockhart, R. M. Post et al., “The emerging role of cytochrome P450 3A in psychopharmacology,” Journal of Clinical Psychopharmacology, vol. 15, no. 6, pp. 387–398, 1995.
- Solvay's Luvox, “Contraindication against co-administration with J&J's Hismanal, MMD's Seldane prompts FDA review of other SSRI labelling,” FDC Reports, The Pink Sheet, 1995.
- R. J. Marchiando, M. D. Cook, and S. G. Jue, “Probable terfenadine-fluoxetine-associated cardiac toxicity,” Annals of Pharmacotherapy, vol. 29, no. 9, pp. 937–938, 1995.
- M. J. Cupp and T. S. Tract, “Cytochrome P450: new nomenclature and clinical implications,” American Family Physician, vol. 57, no. 1, pp. 107–116, 1998.
- D. Gossen, J. M. de Suray, F. Vandenhende, C. Onkelinx, and D. Gangji, “Influence of fluoxetine on olanzapine pharmacokinetics,” AAPS PharmSci, vol. 4, no. 2, p. E11, 2002.
- M. J. Humphrey, S. Jevons, and M. H. Tarbit, “Pharmacokinetic evaluation of UK-49,858, a metabolically stable triazole antifungal drug, in animals and humans,” Antimicrobial Agents and Chemotherapy, vol. 28, no. 5, pp. 648–653, 1985.
- N. K. Wadhwa, T. J. Schroeder, E. O'Flaherty, A. J. Pesce, S. A. Myre, and M. R. First, “The effect of oral metoclopramide on the absorption of cyclosporine,” Transplantation, vol. 43, no. 2, pp. 211–213, 1987.
- D. Lange, J. H. Pavao, J. Wu, and M. Klausner, “Effect of a cola beverage on the bioavailability of itraconazole in the presence of H2 blockers,” Journal of Clinical Pharmacology, vol. 37, no. 6, pp. 535–540, 1997.
- S. Jaruratanasirikul and S. Sriwiriyajan, “Effect of omeprazole on the pharmacokinetics of itraconazole,” European Journal of Clinical Pharmacology, vol. 54, no. 2, pp. 159–161, 1998.
- Y. Kanda, M. Kami, T. Matsuyama et al., “Plasma concentration of itraconazole in patients receiving chemotherapy for hematological malignancies: the effect of famotidine on the absorption of itraconazole,” Hematological Oncology, vol. 16, no. 1, pp. 33–37, 1998.
- A. Johnston, “The pharmacokinetics of voriconazole,” British Journal of Clinical Pharmacology, vol. 56, p. 1, 2003.
- R. A. Blum, D. T. D'Andrea, B. M. Florentino et al., “Increased gastric pH and the bioavailability of fluconazole and ketoconazole,” Annals of Internal Medicine, vol. 114, no. 9, pp. 755–757, 1991.
- G. K. Dresser, D. G. Bailey, B. F. Leake et al., “Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine,” Clinical Pharmacology and Therapeutics, vol. 71, no. 1, pp. 11–20, 2002.
- A. V. Kamath, M. Yao, Y. Zhang, and S. Chong, “Effect of fruit juices on the oral bioavailability of fexofenadine in rats,” Journal of Pharmaceutical Sciences, vol. 94, no. 2, pp. 233–239, 2005.
- S. D. Hall, K. E. Thummel, P. B. Watkins et al., “Molecular and physical mechanisms of first-pass extraction,” Drug Metabolism and Disposition, vol. 27, no. 2, pp. 161–166, 1999.
- E.-J. Wang, K. Lew, C. N. Casciano, R. P. Clement, and W. W. Johnson, “Interaction of common azole antifungals with P glycoprotein,” Antimicrobial Agents and Chemotherapy, vol. 46, no. 1, pp. 160–165, 2002.
- C. M. Pariante, R. B. Kim, A. Makoff, and R. W. Kerwin, “Antidepressant fluoxetine enhances glucocorticoid receptor function in vitro by modulating membrane steroid transporters,” British Journal of Pharmacology, vol. 139, no. 6, pp. 1111–1118, 2003.
Copyright © 2009 Iman Y. Zaghloul et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.