Volume 76, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645


Azithromycin is a critical component of an integrated disease elimination program against trachoma. This study was conducted to evaluate whether azithromycin has a pharmacokinetic interaction with the combination of ivermectin and albendazole. Eighteen healthy volunteers were administered single doses of azithromycin, ivermectin/albendazole, and the combination of the three agents in random, crossover fashion. To assess the presence of interactions, test (combination) and reference (single dose) data were compared using an estimation approach. Compared with reference phases, the geometric mean values for the combination arm’s azithromycin AUC and C were increased approximately 13% and 20%, respectively, albendazole AUC decreased by approximately 3% and C increased approximately 3%, and ivermectin AUC and C were increased 31% and 27%, respectively. Albendazole sulfoxide AUC and C were decreased approximately 16% and 14%, respectively. All treatments were well tolerated. The interactions for azithromycin and albendazole were minimal although the increase in ivermectin exposure requires further study.


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  1. 1998. Global Disease Elimination and Eradication as Public Health Strategies. Bull World Health Org 76 (Suppl 2) : 5–162. [Google Scholar]
  2. Henderson DA, 2002. Smallpox. Knobler S, Lederberg J, Pray LA, eds. Considerations for Viral Disease Eradication: Lessons Learned and Future Strategies: Workshop Summary. Washington, DC: National Academy Press, 33–63.
  3. Technical Consecutive Group, 2002. ‘Endgame’ issues for the global polio eradication initiative. Clin Infect Dis 34 : 72–77. [Google Scholar]
  4. Knirsch C, 2007. Trachoma: ancient scourge, disease elimination, and future research. Curr Infect Dis Rep 9 : 21–28. [Google Scholar]
  5. Mecaskey JW, Knirsch CA, Kumaresan JA, Cook JA, 2003. The possibility of eliminating blinding trachoma. Lancet Infect Dis 3 : 728–734. [Google Scholar]
  6. Ferriman A, 2001. Blinding trachoma almost eliminated from Morocco. BMJ 323 : 1387. [Google Scholar]
  7. Solomon AW, Holland MJ, Alexander ND, Massae PA, Aguirre A, Natividad-Sancho A, Molina S, Safari S, Shao JF, Courtright P, Peeling RW, West SK, Bailey RL, Foster A, Mabey DC, 2004. Mass treatment with single-dose azithromycin for trachoma. N Engl J Med 351 : 1962–1971. [Google Scholar]
  8. Mabey DCW, Solomon AW, Foster A, 2003. Trachoma seminar. Lancet 362 : 223–229. [Google Scholar]
  9. Despommier DD, Gwadz R, Hotez P, Knirsch CA, 2005. Parasitic Diseases. New York: Apple Trees Productions LLC, 143–155.
  10. Hotez PJ, Molyneux DH, Fenwick A, Ottesen E, Ehrlich Sachs S, Sachs JD, 2006. Incorporating a rapid-impact package for neglected tropical diseases with programs for HIV/AIDS, tuberculosis, and malaria. PloS Med 3 : e102. [Google Scholar]
  11. Chiu LM, Amsden GW, 2002. Current trachoma treatment methodologies: Focus on advancements in drug therapy. Drugs 62 : 2573–2579. [Google Scholar]
  12. Amsden GW, Nafziger AN, Foulds G, Cabelus LJ, 2000. A study of the pharmacokinetics of azithromycin and nelfinavir when co-administered in healthy volunteers. J Clin Pharmacol 40 : 1522–1527. [Google Scholar]
  13. Schinkel AH, Smit JJ, van Tellingen O, Beijnen JH, Wagenaar E, van Deemter L, Mol CA, van der Valk MA, Robanus-Maandag EC, te Reiele HP, 1994. Disruption of the mouse mdr1a P-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 77 : 491–502. [Google Scholar]
  14. Food and Drug Administration, 1999. In Vivo Drug Metabolism/Drug Interaction Studies – Study Design, Data Analysis, and Recommendations for Dosing and Labelling. Guidance for Industry. Rockville, MD: US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research.
  15. Sugie M, Asakura E, Zhao YL, Torita S, Nadai M, Baba K, Kitaichi K, Takagi K, Hasegawa T, 2004. Possible involvement of the drug transporters P glycoprotein and multidrug resistance-associated protein Mrp2 in disposition of azithromycin. Antimicrob Agents Chemother 48 : 809–814. [Google Scholar]
  16. Ballow CH, Amsden GW, Highet VS, Forrest A, 1998. Pharmacokinetics of oral azithromycin in serum, urine, polymorphonuclear leucocytes and inflammatory vs non-inflammatory skin blisters in healthy volunteers. Clin Drug Invest 15 : 159–167. [Google Scholar]
  17. Amacher DE, Schomaker SJ, Retsema JA, 1991. Comparison of the effects of the new azalide antibiotic, azithromycin, and erythromycin estolate on rat liver cytochrome P-450. Antimicrob Agents Chemother 35 : 1186–1190. [Google Scholar]
  18. Amsden GW, Nafziger AN, Foulds G, 1999. Pharmacokinetics in serum and leukocyte exposures of oral azithromycin, 1,500 milligrams, given over a 3- or 5-day period in healthy subjects. Antimicrob Agents Chemother 43 : 163–165. [Google Scholar]
  19. Amsden GW, Gray CL, 2001. Serum and WBC pharmacokinetics of 1500 mg of azithromycin when given either as a single dose or over a 3 day period in healthy volunteers. J Antimicrob Chemother 47 : 61–66. [Google Scholar]
  20. Tracy JW, Webster LT Jr, 2001. Drugs used in the chemotherapy of helminthiasis. Hardman JG, Limbird LE, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics. 10th edition. New York: McGraw-Hill, 1121–40.
  21. Nagy J, Schipper HG, Koopmans RP, Butter JJ, van Boxtel CJ, Kager PA, 2002. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg 66 : 260–263. [Google Scholar]
  22. Edwards G, Dingsdale A, Helsby N, Orme MLE, Breckenridge AM, 1988. The relative systemic availability of ivermectin after administration as capsule, tablet, and oral solution. Eur J Clin Pharmacol 35 : 681–684. [Google Scholar]
  23. Baraka OZ, Mahmoud BM, Marschke CK, Geary TG, Homeida MM, Williams JF, 1996. Ivermectin disposition in the plasma and tissues of patients infected with Onchocerca volvulus. Eur J Clin Pharmacol 50 : 407–410. [Google Scholar]
  24. Okonkwo PO, Ogbuokiri JE, Ofoegbu E, Klotz U, 1993. Protein binding and ivermectin estimations in patients with onchocerciasis. Clin Pharmacol Ther 53 : 426–430. [Google Scholar]
  25. Awadzi K, Edwards G, Duke BOL, Opoku NO, Attah SK, Addy ET, Ardrey AE, Quartey BT, 2003. The co-administration of ivermectin and albendazole—safety, pharmacokinetics and efficacy against Onchocerca volvulus. Ann Trop Med Parasitol 97 : 165–178. [Google Scholar]
  26. Guzzo CA, Furtek CI, Porras AG, Chen C, Tipping R, Clineschmidt CM, Sciberras DG, Hsieh JY-K, Lasseter KC, 2002. Safety, tolerability, and pharmacokinetics of escalating high doses of ivermectin in healthy adult subjects. J Clin Pharmacol 42 : 1122–1133. [Google Scholar]

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  • Received : 24 Apr 2006
  • Accepted : 10 Mar 2007

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