Skip to main content
SpringerLink
Log in

Prospective Use of Population Pharmacokinetics/ Pharmacodynamics in the Development of Cisatracurium

  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose. The population PK/PD approach was prospectively used to determine the PK/PD of cisatracurium in various subgroups of healthy surgical patients.

Methods. Plasma concentration (Cp) and neuromuscular block data from 241 patients in 8 prospectively-designed Phase I−III trials were pooled and analyzed using NONMEM. The analyses included limited Cp-time data randomly collected from 186 patients in efficacy/safety studies and full Cp-time data from 55 patients in pharmacokinetic studies. The effects of covariates on the PK/PD parameters of cisatracurium were evaluated. The time course of neuromuscular block was predicted for various patient subgroups.

Results. The population PK/PD model for cisatracurium revealed that anesthesia type, gender, age, creatinine clearance, and presence of obesity were associated with statistically significant (p < 0.01) effects on the PK/PD parameters of cisatracurium. These covariates were not associated with any clinically significant changes in the predicted recovery profile of cisatracurium. Slight differences in onset were predicted in patients with renal impairment and patients receiving inhalation anesthesia. Based on the validation procedure, the model appears to be accurate and precise.

Conclusions. The prospective incorporation of a population PK/PD strategy into the clinical development of cisatracurium generated information which influenced product labeling and reduced the number of studies needed during development.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. C. Lee, B. K. Tran. In S. M. Rupp, R. R. Kirby, D. L. Brown (eds), Problems in Anesthesia Vol 3,No. 3, J. B. Lippincott Company, Maryland 1989, pp. 379–393.

    Google Scholar 

  2. S. Beal, L. B. Sheiner, eds. NONMEM user's guides 1992, NONMEM Project Group, University of California at San Francisco, San Francisco.

  3. C. C. Peck, D. P. Conner, and M. G. Murphy. Bedside clinical pharmacokinetics. Applied Therapeutics, Inc. Revised edition, 1991:81.

  4. D. Kisor, V. D. Schmith, W. A. Wargin, et al. Anesth Analg, 83:1065–71 (1996).

    PubMed  Google Scholar 

  5. R. Welch, A. Brown, and R. Dahl. Clin Pharmacol Ther, 58:132–4 (1995).

    PubMed  Google Scholar 

  6. L. B. Sheiner and S. L. Beal. J Pharmacokin Biopharm 9(4):503–11 (1981).

    Google Scholar 

  7. Currently approved labeling for Nimbex® Injection, DNA 20–551.

  8. S. J. L. Riegelman and M. Rowland. J Pharm Sci 57(1):128–33 (1968).

    PubMed  Google Scholar 

  9. E. I. Eger. The pharmacology of isoflurane. Br J Anesth 56:71S–99S (1984).

    Google Scholar 

  10. E. Ornstein, C. A. Lien, R. S. Matteo, et al. Anesthesiology 84:520–5 (1996).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Clinical Pharmacokinetics and Dynamics, Glaxo Wellcome Inc., 5 Moore Drive, RTP, North Carolina, 27709

    Virginia D. Schmith

  2. Pharmaceutical Outcomes Research, Inc., 435 Lawrence Bell Drive, Williamsville, New York, 14221

    Jill Fiedler-Kelly, Luann Phillips & Thaddeus H. Grasela Jr.

Authors
  1. Virginia D. Schmith
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jill Fiedler-Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Luann Phillips
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Thaddeus H. Grasela Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Virginia D. Schmith.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schmith, V.D., Fiedler-Kelly, J., Phillips, L. et al. Prospective Use of Population Pharmacokinetics/ Pharmacodynamics in the Development of Cisatracurium. Pharm Res 14, 91–97 (1997). https://doi.org/10.1023/A:1012015719694

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1012015719694

Search

Navigation