Metabolism and Tissue Residues

  • Shuet-Hing Lee Chiu
  • Anthony Y. H. Lu


Ivermectin is used widely as an antiparasitic agent in food-producing animals. As in the case of any such drug, the residual tissue concentration of the therapeutic agent, or tissue residue, is a safety concern to the meat-consuming public. To evaluate the toxic potential of the residual tissue concentration of ivermectin and its metabolites, metabolism studies have been carried out in target species (cattle, sheep, swine) using the radiolabeled drug. Comparative metabolic studies were done in a laboratory animal, the rat, and in liver microsomes from various species.


Liver Microsome Parent Drug Fatty Acid Ester Polar Metabolite Post Dose 
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. Caldwell J, Marsh MV (1983) Interrelationships between xenobiotic metabolism and lipid biosynthesis. Biochem. Pharm. 32:1667–1672PubMedCrossRefGoogle Scholar
  2. Campbell WC, Fisher MH, Stapley EO, Albers-Schonber G, Jacob TA (1983) Ivermectin: A potent new antiparasitic agent. Science 221:923–928Google Scholar
  3. Chiu SHL, Buhs RP, Sestokas E, Taub R, Jacob TA (1985) Determination of ivermectin residue in animal tissues by high performance liquid chroma- tography-reverse isotope dilution assay. J. Agric. Food Chem. 33:99–102CrossRefGoogle Scholar
  4. Chiu SHL, Carlin JR, Taub R, Sestokas E, Zweig J, VandenHeuval WJA, Jacob TA (1988) Comparative metabolic disposition of ivermectin in fat tissues of cattle, sheep, and rats. Drug Me tab. & Dispos. 16:728–736Google Scholar
  5. Chiu SHL, Sestokas E, Taub R, Buhs RP, Green M, Sestokas R, VandenHeuvel WJA, Arison BH, Jacob TA (1986) Metabolic disposition of ivermectin in tissues of steers, sheep, and rats. Drug Metab. & Dispos. 14:590–600Google Scholar
  6. Chiu SHL, Sestokas E, Taub R, Smith JL, Arison B, Lu AYH (1984) The metabolism of avermectin-H2B1a and -H2B1b by pig liver microsomes. Drug Metab. & Dispos. 12:464–469Google Scholar
  7. Chiu SHL, Taub R, Sestokas E, Lu AYH, Jacob TA (1987) Comparative in vivo and in vitro metabolism of ivermectin in steers, sheep, swine, and rat. Drug Metab. Rev. 18:289–302PubMedCrossRefGoogle Scholar
  8. Dell HD, Fiedler J, Kamp R, Gaug W, Kurz J, Weber B, Wuensche C (1982) Etofenamate fatty acid esters, an example of a new route of drug metabolism. Drug Metab. & Dispos. 10:55–60Google Scholar
  9. Dorough HW (1980) Classification of radioactive pesticide residues in food- producing animals. J. Environ. Path. Toxicol. 3:11–19Google Scholar
  10. Jacob TA, Buhs RP, Carlin JR, Chiu SHL, Miwa GT, Rosegay A (1983) The metabolism and tissue residue profiles of ivermectin. In Proceedings of the MSD AGVET Symposium on Recent Developments in the Control of Animal Parasites, XXII World Veterinary Congress, Perth, AustraliaGoogle Scholar
  11. Leighty EG, Fentiman Jr AF, Foltz RL (1976) Long-chain metabolites of Δ9- and Δ8-tetrahydrocannabinols identified as novel fatty acid conjugates. Res. Comm. Chem. Pathol. Pharm. 14:13–28Google Scholar
  12. Lu AYH, Wislocki PG, Chiu SHL, Miwa GT (1987) Tissue drug residues and their toxicological significance. Drug Metab. Reviews 18:363–378CrossRefGoogle Scholar
  13. Miwa GT, Walsh JS, VandenHeuvel WJA, Arison B, Sestokas E, Buhs R, Rosegay A, Avermitilis S, Lu AYH, Walsh MAR, Walker RW, Taub R, Jacob TA (1982) The metabolism of avermectins B1a, H2B1a and H2B1b by liver microsomes. Drug Metab. & Dispos. 10:268–274Google Scholar
  14. Pivnichny JV, Shim J-SK, Zimmerman LA (1983) Direct determination of avermectins in plasma at nanogram levels by high-performance liquid chromatography. J. Pharm. Sci. 72:1447–1450PubMedCrossRefGoogle Scholar
  15. Schmid J, Prox A, Baeur E, Koss FW (1980) Abstract No. 434, 7th European Workshop on Drug Metabolism, ZurichGoogle Scholar
  16. Stong JD (1987) Determination of ivermectin by fluorescence derivatization. Anal. Chem. 59:266–270PubMedCrossRefGoogle Scholar
  17. Tolan JW, Eskola P, Fink DW, Mrozik H, Zimmerman LA (1980) Determination of avermectin in plasma at nanogram levels using high-performance liquid chromatography with fluorescence detection. J. Chromatogr. 190:367–376PubMedCrossRefGoogle Scholar
  18. Tway PC, Wood Jr JS, Downing GV (1981) Determination of ivermectin in steers and sheep tissues using high-performance liquid chromatography with fluorescence detection. J. Agric. Food Chem. 29:1059–1063PubMedCrossRefGoogle Scholar
  19. Weber NE (1980) Persistent residues: Interface with regulatory decisions. J. Environ. Path. Toxicol. 3:35–43Google Scholar

Copyright information

© Springer-Verlag New York Inc. 1989

Authors and Affiliations

  • Shuet-Hing Lee Chiu
    • 1
  • Anthony Y. H. Lu
    • 1
  1. 1.Department of Animal Drug MetabolismMerck Sharp & Dohme Research LaboratoriesRahwayUSA

Personalised recommendations