Time to Reach the Maintenance (Plateau) State

How long does it take to reach the maintenance state? The half time for rising, t ½, is equal to the old elimination t_½ that we saw before. This is called the Plateau Principle.

The Plateau Principle means that in one t_½, the concentration gets half way to the top (C_max), in 2 half lives it gets ¾ of the way (75%), in 3 half lives it gets 87.5% C_max, in 4 half lives it gets to 93.75%, etc.

The general rule is that 94% C_max is considered to be close enough for therapeutic purposes, so it takes 4 half lives (4 t_½) to reach the maintenance state.

Example: For tetracycline, where t_½ is 6 hours, the time to reach 94% of the maintenance level (assuming a constant repetitive dose) is 4 x 6 = 24 hrs.

But what if we don’t dare to wait 24 hours until an effective dose is reached? (see handout p. 13)

We could give one dose of 500 mg right away to get the patient right up there, then maintain it at 250mg each 6 hrs, or whatever the maintenance schedule is. This is the Loading (Priming) Dose.

Why not always do that? It can only be done with a high therapeutic index, when the drug is very safe. If the drug isn’t very safe, the patient may be adversely affected.

The first loading dose (C_L) brings the amount of drug in the body to the level of C_L. At t_½ this amount has decayed to ½ C_L. So addition of a second dose C_L at this time now brings the total to ½ C_L + C_L = 3/2 C_L. When we know the peak maintenance level that we want, we can make that amount equal to 3/2 C_L, and solve for C_L.

Category: Pharmacology Notes