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<strong>Pharmacokinetics</strong>Constant intravenous infusionFinally, at (C), the body load has risen sufficiently for the rate of elimination to match that of infusion. From this pointon, the two processes are in balance and blood levels settle down. This situation is referred to as ‘Steady state’ and theassociated blood concentration is ‘Concentration at steady state’ or Css.4.543.5Css(C) Elim = R infConc (mg/L)32.521.5(B) Elim < R inf10.50(A) Elim
<strong>Pharmacokinetics</strong>Constant intravenous infusion8.3.2 Determination of clearance as part of the drug development processBecause the equation linking Css to Rinf is general, infusion offers a definitive method for the measurement of clearance.If it is possible to arrange to deliver a new drug by infusion for a period long enough to achieve steady state, a re-arrangedform of the standard equation (below) can be used to determine clearance:Cl = Rinf / CssClearance values obtained by this method are free of any considerations as to how many compartments the drug mightoccupy.8.4 Loading doses8.4.1 Loading dose where drugs are treated as occupying one compartmentIn Figure 8.3, the useful therapeutic range of a drug is between 3 and 5 mg/L and this is indicated by shading. Concentrationsbelow or above this range are likely to be either ineffective or toxic respectively. With a simple infusion (indicated as ‘Noloading dose’) the patient will achieve an inadequate therapeutic effect for approximately the first six hours of treatment.With some drugs this might be tolerable. However, with an anti-asthmatic drug such as theophylline (which may be givenby infusion) we certainly could not leave the patient unable to breathe properly for such a long time.Please click the advertJoin the VestasGraduate ProgrammeExperience the Forces of Windand kick-start your careerAs one of the world leaders in wind power solutionswith wind turbine installations in over 65countries and more than 20,000 employeesglobally, Vestas looks to accelerate innovationthrough the development of our employees’ skillsand talents. Our goal is to reduce CO 2emissionsdramatically and ensure a sustainable world forfuture generations.Read more about the Vestas GraduateProgramme on vestas.com/jobs.Application period will open March 1 2012.Download free ebooks at bookboon.com75
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