In most clinical situations, drugs are administered in a series of repetitive doses or as a continuous infusion to maintain a steady-state concentration of drug associated with the therapeutic window. Calculation of the appropriate maintenance dosage is a primary goal. To maintain the chosen steady-state or target concentration, the rate of drug administration is adjusted such that the rate of input equals the rate of loss. This relationship is expressed here in terms of the desired target concentration:
If the clinician chooses the desired concentration of drug in plasma and knows the clearance and bioavailability for that drug in a particular patient, the appropriate dose and dosing interval can be calculated.
In general, marked fluctuations in drug concentrations between doses are not desirable. If absorption and distribution were instantaneous, fluctuations in drug concentrations between doses would be governed entirely by the drug's elimination tm. If the dosing interval T were chosen to be equal to the ty2, then the total fluctuation would be twofold; this is often a tolerable variation.
Pharmacodynamic considerations modify this. For drugs with a narrow therapeutic range, it may be important to estimate the maximal and minimal concentrations that will occur for a particular dosing interval. The minimal steady-state concentration C . may be reasonably deter° y ss.min J J
mined by the use of Equation (1-13):
where k equals 0.693 divided by the clinically relevant plasma t/2 and T is the dosing interval. The term exp(-kT) is, in fact, the fraction of the last dose (corrected for bioavailability) that remains in the body at the end of a dosing interval.
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