Dosing intervals multiple intravenous boluses

If drug had been administered in equally sized multiple intravenous bolus doses at equally spaced t time intervals (e.g., t = 6 h), then an accounting of accumulated drug between doses must be instituted. Figure 1.18, similar to the zero-order input, shows that repetitive instantaneous dosing will produce an average Cp profile similar to Fig. 1.17. 

Figure 11.9 Plasma concenfration (Cp) versus time profile following the administration of multiple intravenous bolus doses of a drug, min, minimum max, maximum av, average t, dosing interval.

This expression, which relies on fairly rapid absorption such that each subsequent dose is administered in the post-absorptive phase, can be readily employed to determine the extent of accumulation following extravascular administration of a drug as long as dosing interval and the elimination rate constant of the drug are available. Note the similarity between Eq. 12.27 for multiple oral dosing and Eqs 11.29,11.33 and 11.34 for multiple intravenous bolus administration. 

Notice that Eq. 12.43 includes two different dosing intervals tjv in the numerator and Xorai in the denominator Torai is the known interval for a satisfactory oral dosing regimen. In order to control fluctuation for the new multiple intravenous bolus dosing regimen, it is necessary to calculate a smaller (shorter) value for tiv and then insert this value into the numerator of Eq. 12.43. Since this means that the intravenous bolus will be given more frequently, and since (Cave)ss should... 

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