Pharmacoepidemiology, Population Pharmacokinetics and New Drug Development

  • Thaddeus H. GraselaJr.
  • Edward J. Antal

Abstract

It is important to recognize that the new drug development process, which begins with the identification of a potential therapeutic compound, continues well into the post-marketing period. The responsibility of regulators, scientists, physicians, and the pharmaceutical industry to pursue knowledge about drug safety and efficacy extends well beyond the time when sufficient information is available to suggest that a drug is safe and efficacious, and warrants marketing. The ultimate uses of newly marketed medications and the clinical milieu into which it will be interposed is extremely dynamic and complex. It is during the early marketing period that a number of drugs approved for marketing were discovered to have serious, unanticipated adverse events requiring at best a change in labeling; and at worst removal from the market at great cost, in terms of credibility and dollars, to both FDA and the pharmaceutical industry (FDA Drug Review, 1990).

Keywords

Placebo Toxicity Depression Marketing Theophylline 

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References

  1. Antal, E. J., T. H. Grasela, and R. B. Smith (1989). An evaluation of population pharmacokinetics in therapeutic trials Part III. Prospective data collection versus retrospective data assembly. Clin. Pharmacol. Ther. 46, 552–559.PubMedCrossRefGoogle Scholar
  2. Antal, E. J., D. A. Pyne, K. E. Starz, and R. B. Smith (1988). Probability models in pharmacodynamic analysis of clinical trials. In P. Kroboth and R. B. Smith (Eds.), Current Problem and Potential Solutions. Vol. 2. Harvey Whitney Books, Cincinnati. pp. 220–231.Google Scholar
  3. Beal, S. L., and L. B. Sheiner (1982). Estimating population kinetics. CRC Crit. Rev. Biomed. Engineering 8, 195–222.Google Scholar
  4. Beal, S. L., and L. B. Sheiner (Eds.), (1983). NONMEM Users Guide - Part VI: PREDPP Guide. NONMEM Project Group, University of California at San Francisco, San Francisco, CA.Google Scholar
  5. FDA Drug Review (1990). Post-approval risks 1976–85. United States General Accounting Office, Report to the Chairman, subcommittee on Human Resources and Intergovernmental Relations, Committee on Government Operations, House of Representatives. PEMD–90–15.Google Scholar
  6. Grasela, T. H., and M. W. Dreis (1992). An evaluation of the quinolone-theophylline interaction using the FDA Spontaneous Reporting System. Arch. Intern. Med., 152 617–621.PubMedCrossRefGoogle Scholar
  7. Holford, N. H. G., and L. B. Sheiner (1981). Understanding the dose-effect relationship: clinical application of pharmacokinetic-pharmacodynamic models. Clin. Pharmacokinet. 6 429–453.PubMedCrossRefGoogle Scholar
  8. Hosmer, D. W., and S. Lemeshow (Eds.), (1989). Applied Logistic Regression. John Wiley and Sons. New York.Google Scholar
  9. Lee, E. T. (1980). Statistical Methods for Survival Data Analysis. Lifetime Learning Publication, Belmont, CA.Google Scholar
  10. Ludden, T. M. (1988). Population pharmacokinetics. J. Clin. Pharmacol. 28, 1059–1063.PubMedCrossRefGoogle Scholar
  11. MacMahon, B., and T. F. Pugh (Eds.), (1970), Epidemiology Principles and Methods Little, Brown and Company, Boston.Google Scholar
  12. Peck, C. C., and J. H. Rodman (1986). Analysis of clinical pharmacokinetic data for individualizing drug dosage regimens. In W. E. Evans, J. J. Schentag, and W. J. Jusko (Eds.), Applied Pharmacokinetics 2nd edition, Applied Therapeutics, Inc., Spokane, WA, pp. 55–82.Google Scholar
  13. Sheiner, L. B., and S. L. Beal (1983). Evaluation of methods for estimating population pharmacokinetic parameters. III. Monoexponential model: Routine clinical pharmacokinetic data. J. Pharmacokinet. Biopharm. 3, 303–319.Google Scholar
  14. Sheiner, L. B., and L. Z. Benet (1985). Premarketing observational studies of population phannacokinetics of new drugs. Clin. Pharmacol. Ther. 38, 481–487.PubMedCrossRefGoogle Scholar
  15. Strom, B. L. (Ed.), (1989). Pharrnacoepidemiology. Churchill Livingstone, New York.Google Scholar

Copyright information

© Springer Science+Business Media New York 1993

Authors and Affiliations

  • Thaddeus H. GraselaJr.
    • 1
  • Edward J. Antal
    • 2
  1. 1.Department of Pharmacy and Social and Preventive Medicine Schools of Pharmacy and MedicineState University of New York BuffaloBuffaloUSA
  2. 2.Clinical PharmacokineticsThe Upjohn CompanyKalamazooUSA

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