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


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 


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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

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