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Metabolic disposition of rolziracetam* in laboratory animals

  • A. Black
  • T. Chang
Original Papers

Summary

The metabolic disposition of [l4C]-labeled Rolziracetam (CI-911) was studied in rhesus monkeys, beagle dogs, and Wistar rats after both p.o. and i.v. doses. Intravenously administered CI-911 was rapidly eliminated from systemic circulation with an apparent elimination half-life of less than 25 min. Plasma radioactivity was 10–20 times higher than that of parent drug and persisted much longer. After oral doses, only traces of intact drug were detected in plasma, whereas total radioactivity reached peak concentrations within 0.5–1 h indicating rapid absorption. The extent of absorption determined from plasma radioactivity and urinary excretion data was 90% or better. Tissue distribution of radioactivity in rats showed the highest concentrations in the liver and kidneys (12–30 times greater than plasma levels) with decreasing levels in the lungs, gonads, heart, spleen, muscle, and brain. Urinary excretion accounted for nearly 90% of the administered dose while fecal recovery was less than 5%. The sole metabolite present in plasma, tissues, and urine was identified as 5-oxo-2-pyrrolidinepropanoic acid (PD 106,687).

Key-words

Rolziracetam nootropic metabolism pharmacokinetics laboratory animals 

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References

  1. 1.
    Marriott J.G., Poschel B.P.H. Voigtman, R.E. Abelson, J.S. and Butler D.E.; (1984): Cognition activiation of properties of dihydro-lH-pyrrolizine-3,5-(2H,6H)-dione (CI-911) in animal models. Society for Neuroscience Abstracts. Vol.10 (Part 1) 252.Google Scholar
  2. 2.
    Sedman A.J. and Wagner J.G. (1976): AUTOAN Program, University of Michigan, Ann Arbor 48016, used conjunction with CM. Metzer, G.L. Elping and A.J. McEvan, A users manual for NONLIN and associated programs (1974). Research Biostatistics. The Upjohn Co., Kalamazoo, Michigan.Google Scholar
  3. 3.
    Benet L.Z. and Galeagzi R.L. (1979): Noncompartmental determination of the steady state volume of distribution. J. Pharm Sci.68, 1071–1074.CrossRefPubMedGoogle Scholar
  4. 4.
    Heyman E. (1980): Carboxylestrases and Amidases. In “Enzymatic Basis of Detoxification II” (W.B. Jakoby ed.), 292–294. Academic Press, New York.Google Scholar
  5. 5.
    Pfeifer S. (1968): Biotransformation of Drugs. Pharmazie23, 225–236.PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • A. Black
    • 1
  • T. Chang
    • 1
  1. 1.Pharmacokinetic/Drug Metabolism Department, Warner-Lambert/Parke-Davis Pharmacuetical Research DivisionWarner-Lambert CompanyAnn ArborUSA

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