Review Question - QID 106861

The minimum number of hours required to reach a steady state concentration of >90% is 6 hours (4 half lives).

A drug infused at a constant rate reaches about 94% of steady state concentration after 4 half lives when it is eliminated by first order kinetics. A simplified example is as follows: if compound Y (half life of 1 hour) was infused at 100 mg/hr, then after 1 hour, 50% or 50 mg of the drug would be left in circulation. In the next hour, another 100 mg would be infused and a total of 150 mg (100 mg infused + 50 mg from the first hour) would have circulated, but since another hour or half life has passed the total amount remaining in circulation would be 75 mg or 75% of the infusable rate. The calculation is similar for the next two hours where it will reach 93.75% of the steady state concentration by the fourth hour.

Ratain et al. discuss clearance rate as the elimination of a drug from the body. It is represented as clearance = V * K where V is the volume of distribution and K is the elimination constant which is inversely proportional to the half life.

McKay et al. discuss the pharmacokinetics of corticosteroids. Clearance of cortisol is quick with a half life of 66 minutes, but aldosterone is even quicker at < 20 minutes. Metabolism mainly occurs through enzymatic transformation to increase their water solubility to be excreted in the urine.

Incorrect answer:
Answer 1: After 1.5 hours, only 50% of the steady state concentration will be reached.
Answer 2: After 3 hours, only 75% of the steady state concentration will be reached.
Answer 3: After 4.5 hours, only 87.5% of the steady state concentration will be reached.
Answer 5: After 7.5 hours, 96.9% of the steady state concentration will be reached.