Journal of Pharmacokinetics and Biopharmaceutics

, Volume 14, Issue 1, pp 95–106 | Cite as

Relationships among duration of infusion, dose, dosing interval, and steady-state plasma concentrations during intermittent intravenous infusions: Studies with metronidazole

  • Dominic A. Uccellini
  • Denis J. Morgan
  • Kenneth Raymond
Article

Abstract

Relationships among duration of infusion (T), dose, dosing interval (Τ), maximum and minimum plasma drug concentrations at steady state (Cmax,ssand Cmin,ss, respectively), and the duration of effective plasma concentrations (tD) during multidose intermittent infusion regimens were studied by computer simulation using metronidazoie as a model drug. Pharmacokinetic parameter values for metronidazole were obtained from the literature and the minimum effective plasma concentration (MEC) was taken as 6.0 Μg/ ml. Increasing the infusion period of the dose reduces Cmax,ss, but increases Cmin,ss. If intermittent bolus injection of a given dose of drug results in effective plasma concentrations for the entire dosage interval (i.e., Cmin,ss,bolus> MEC), then infusion of that dose over any period (T≤Τ) will also result in effective concentrations for the entire dosage interval. However, if the dosage is such that Cmin,ss,bolus < MEC, the relationships among duration of infusion, dose, dosage interval, and duration of effective plasma concentrations are complex. Therefore a nomogram was developed to allow selection of dose, dosing interval, and infusion period such that Cmax,ss and Cmin,ss could be maintained within a desired range.

Key words

intravenous infusion plasma concentration-time curves infusion rate minimum effective plasma concentration intermittent infusions steady-state dosing interval 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    K. Raymond and D. J. Morgan. The effect of infusion time on the time course of drug concentration in blood.J. Pharmacokin. Biopharm. 8:573–582 (1980).CrossRefGoogle Scholar
  2. 2.
    D. J. Morgan and K. Raymond. The effect of duration of intravenous infusion on maximum and threshold blood concentrations for drugs exhibiting biexponential elimination kinetics.J. Pharmacokin. Biopharm. 10:93–107 (1982).CrossRefGoogle Scholar
  3. 3.
    A. P. Ball and J. A. Gray.Antibacterial Drugs Today, Adis Health Science Press, Sydney, 1983, p. 97.Google Scholar
  4. 4.
    J. G. Wagner. Linear pharmacokinetic equations allowing direct calculation of many needed pharmacokinetic parameters from the coefficients and exponents of polyexponential equations which have been fitted to the data.J. Pharmacokin. Biopharm. 4:443–467 (1976).CrossRefGoogle Scholar
  5. 5.
    M. Gibaldi and D. Perrier.Pharmacokinetics, Marcel Dekker, New York, 1982.Google Scholar
  6. 6.
    H. R. Rabin, R. C. Urtasun, J. Partington, D. Koziol, M. Sharon, and K. Walker. High dose metronidazole: Pharmacokinetics and bioavailability using an I.V. preparation and application of its use as radiosensitizer.Cancer Treat. Rep. 64:1087–1095 (1980).PubMedGoogle Scholar
  7. 7.
    A. W. Chow, V. Patten, and L. B. Gouze. Susceptibility of anaerobic bacteria to metronidazole: Relative resistance of non-spore-forming Gram-positive bacilli.J. Infect. Dis. 131:182–185 (1975).PubMedCrossRefGoogle Scholar
  8. 8.
    R. E. Notari, M. Huang, and P. R. Byron. Calculations of optimum pharmacokinetic drug supply rates for maximum duration during multiple dose therapy by prodrug administration.Int. J. Pharm. 1:233–247 (1978).CrossRefGoogle Scholar

Copyright information

© Plenum Publishing Corporation 1986

Authors and Affiliations

  • Dominic A. Uccellini
    • 1
  • Denis J. Morgan
    • 1
  • Kenneth Raymond
    • 1
  1. 1.Victorian College of PharmacyMelbourneAustralia

Personalised recommendations