If the loading dose over- or under -shoots the steady state concentration, it will still take 3-5 half -lives to reach C ss (see Article 2), but the initial concentration will be closer to the eventual steady state concentration.
If the loading dose achieves a plasma drug concentration the same as the steady state concentration for the maintenance infusion (see equation 1), steady state will be immediately achieved and maintained. The therapeutic range for theophylline is 10-20 mg/L (55-110 mmol/L). Same as that during a continuous infusion (14.4 mg/L in this case). At steady state, the average plasma concentration over the dosing interval is the Parameters used in the simulations were: CL = 2.6 L/hour, V D = 30 L, t 1/2 = 8 hours. (c) As for (b) but with a loading dose of 600 mg, twice the maintenance dose (b) Intermittent bolus dosing 300 mg 8-hourly (dose rate (dose/dosing interval) is 37.5 mg/hour) (a) Continuous intravenous infusion at a dose rate of 37.5mg/hour Intravenous infusion or intermittent dosing of a drug such as theophylline. Loading dose = desired concentration x V D The loading dose to achieve a desired concentration is determined by the volume of distribution (VD). The effect of a loading dose before an intravenous infusion has been discussed in Article 2 ('Volume of distribution' Aust Prescr 1988 11:36-7).
Given as a continuous infusion, the drug accumulates to a steady state concentration (C ss) determined only by the dose rate and clearance (CL) (see Article 1 'Clearance' Aust Prescr 1988 11:12-3). 1 illustrates the plasma concentration time course of theophylline given intravenously. Intravenous infusion and intermittent intravenous bolus dosingĬontinuous intravenous infusions and intermittent intravenous boluses are common ways of administering drugs such as gentamicin, lignocaine and theophylline.
Information from previous articles in this series can be used to design dose regimens.ġ.