Veterinary Research Communications

, Volume 9, Issue 1, pp 251–268 | Cite as

Pharmacokinetic studies of ivermectin: Effects of formulation

  • Pak-Kan Albert Lo
  • David W. Fink
  • James B. Williams
  • Jack Blodinger
Research Articles


Studies are reported which describe the effects of formulation, animal species, and route of administration on the pharmacokinetics of ivermectin. Biological half-life t1/2 increases in the order: swine (0.5 day) > dogs (1.8 day) > cattle ≌ sheep (2.8 day). Formulation modifications, based upon the solubility properties of the drug, have been directed towards the development of a nonaqueous injectable formulation for cattle and an aqueous vehicle for horses. Bioavailability following subcutaneous injection in cattle can be regulated by control of injection solvent composition: a vehicle composed of a mixed aqueous-organic solvent exhibits pharmacokinetic properties (i.e., Cp, t1/2, AUC, and F) intermediate between those furnished by an aqueous formulation and via a purely nonaqueous solvent. The longer apparent biological half-life from this latter vehicle (t1/2=8.3 days) confirms that a slow absorption process dominates the pharmacokinetics in the nonaqueous injectable product to produce an effective controlled-release formulation. These bioavailability results illustrate the increase in the concentration of an organic solvent and a concomitant decrease in surfactant concentration in a micellar aqueous system for prolonged drug delivery via injection.


Surfactant Concentration Pharmacokinetic Property Absorption Process Ivermectin Concomitant Decrease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albers-Schönberg, G., Arison, B. H., Chabala, J. C., Douglas, A. W., Eskola, P., Fisher, M. H., Lusi, A., Mrozik, H., Smith, J. L. and Tolman, R. L., 1981. Avermectins. Structure determination. Journal of the American Chemical Societv, 103: 4216–4221.Google Scholar
  2. Anderson, D. L. and Roberson, E. L., 1982. Activity of ivermectins against canine intestinal helminths. American Journal of Veterinary Research, 43: 1681–1683.Google Scholar
  3. Armour, J., Bairden, K. and Preston, J. M., 1982. Anthelmintic efficiency of iveragainst naturally occurring gastrointestinal nematodes of sheep. Veterinary Record, 111: 80–81.Google Scholar
  4. Campbell, W. C. 1982. Efficacy of the avermectins against filarial parasites: A short review. Veterinary Research Communications, 5: 251–262.Google Scholar
  5. Campbell, W. C. and Benz, G. W., 1984. Ivermectin: a review of efficacy and safety. Journal of Veterinary Pharmacology and Therapeutics, 7: 1–16.Google Scholar
  6. Campbell, W. C., Fisher, M. H., Stapley, E. O., Albers-Schönberg, G. and Jacob, T. A., 1983. Ivermectin: A potent new antiparasitic agent. Science, 221: 823–828.Google Scholar
  7. Chabala, J. C., Mrozik, H., Tolman, R. L., Eskola, P., Lusi, A., Peterson, L. H., Woods, M. F. and Fisher, M. H., 1980. Ivermectin, a new broad-spectrum antiparasitic agent. Journal of Medical Chemistry, 23: 1134–1136.Google Scholar
  8. Courtnev, C. H., Ingals, W. L., and Stitzlein, S. L. 1983. Ivermectin for the control of swine scabies: Relative values of prefarrowing treatment of sows and weaning treatment of pigs. American Journal of Veterinary Research, 44: 1220–1223.Google Scholar
  9. Hibbert, H. and Carter, N. M., 1928. Studies on the reactions relating to carbohydrates and polysaccharides. XVII. Structure of the isomeric methylidene glycerols. Journal of the American Chemical Society, 50: 3120–3127.Google Scholar
  10. Leo, A., Hansch, C. and Elkins, D., 1971. Partition coefficients and their uses. Chemical Reviews, 71: 525–555.Google Scholar
  11. Lo, P.-K. A. and Williams, J. B., 1983. Solubilization of ivermectin in water. U. S. Patent 4,389,397. Chemical Abstracts, 99:76906q.Google Scholar
  12. Meleney, W. P. 1982. Control of psorootic scabies on calves with ivermectin. American Journal of Veterinary Research, 43: 329–331.Google Scholar
  13. Mirck, M. H. and vanMeurs, G. K., 1982. The efficacy of ivermectin against strongyloides westeri in foals. Veterinary Quarterly, 4: 89–91.Google Scholar
  14. Notari, R. E., 1980. Biopharmaceutics and clinical pharmacokinetics. An Introduction. Third Edition, Marcel Dekker, Inc., New York, p. 127.Google Scholar
  15. Pivnichny, J. V., Shim, J.-S.K. and Zimmerman, L. A. 1983. Direct determination of avermectins in plasma at nanogram levels by high-performance liquid chromatography. Journal of Pharmaceutical Sciences, 72: 1447–1450.Google Scholar
  16. Tolan, J. W., Eskola, P., Fink, D. W., Mrozik, H. and Zimmerman, L. A., 1980. Determination of avermectins in plasma at nanogram levels using highperformance liquid chromatography with fluorescence detection. Journal of Chromatography, 190: 367–376.Google Scholar

Copyright information

© Elsevier Science Publishers B.V 1985

Authors and Affiliations

  • Pak-Kan Albert Lo
    • 1
  • David W. Fink
    • 1
  • James B. Williams
    • 1
  • Jack Blodinger
    • 1
  1. 1.Merck Sharp and Dohme Research LaboratoriesRahway(U.S.A.)

Personalised recommendations