TAILIEUCHUNG - CLINICAL PHARMACOLOGY 2003 (PART 9B)

If a drug is administered by constant-rate . infusion it is important to know when steady state has been reached, for maintaining the same dosing schedule will then ensure a constant amount of drug in the body and the patient will experience neither acute toxicity nor decline of effect. The t1/2 provides the answer: with the passage of each t1/2 period of time, the plasma concentration rises by half the difference between the current concentration and the ultimate steady-state (100%) concentration. . | GENERAL PHARMACOLOGY SECTION 2 Time to reach steady state If a drug is administered by constant-rate . infusion it is important to know when steady state has been reached for maintaining the same dosing schedule will then ensure a constant amount of drug in the body and the patient will experience neither acute toxicity nor decline of effect. The tj provides the answer with the passage of each t period of time the plasma concentration rises by half the difference between the current concentration and the ultimate steady-state 100 concentration. Thus in 1 x tj the concentration will reach 100 2 50 in 2 x t 2 50 50 2 75 in 3 x t 2 75 25 2 in 4 x t 2 2 in 5 x t 2 2 of the ultimate steady state. When a drug is given at a constant rate continuous or intermittent the time to reach steady state depends only on the t i and. for all practical purposes after S x t 2 the amount of drug in the body will be constant and the plasma concentration will be at a plateau. Changes in plasma concentration The same principle holds for change from any steady-state plasma concentration to a new steady state brought about by increase or decrease in the rate of drug administration provided the kinetics remain first-order. Thus when the rate of administration is altered to cause either a rise or a fall in plasma concentration a new steady-state concentration will eventually be reached and it will take a time equal to 5 x t1 to reach the new steady state. Note that the actual level of any steady-state plasma concentration as opposed to the time taken to reach it is determined only by the difference between the rate of drug administration input and the rate of elimination output . If drug elimination remains constant and administration is increased by 50 in time a new steady-state concentration will be reached which will be 50 greater than the original. Decline in plasma concentration Since t is the time taken for any plasma concentration to decline by

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