3.9:
Time Course of Drug Effect
The time course of drug effect is described based on the concentration-time course and the effect-time course.
The concentration-time course depends on the drug's half-life. The effect is calculated based on the maximum drug effect and the plasma concentration producing 50% of the maximal effect.
Consider a bolus drug dose with a 3-hour half-life and 1 ng/ml C50 value. The peak plasma concentration is 64 ng/ml at 3 hours.
At 24 hours, the drug plasma concentration is below 1% of the peak concentration. This is half the value of C50, with only 33% ACE inhibition.
If the concentration is above C80 the effect change is negligible despite changes in concentration, and the curve is almost flat.
If the concentration is between C80 and C20, the effect curve is almost a straight line.
If the concentration is below C20, the curves are almost parallel.
3.9:
Time Course of Drug Effect
The progression of a drug's impact can be analyzed by examining both the concentration-time course and the effect-time course. The concentration-time course is determined by the drug's half-life and is influenced by factors such as its pharmacokinetics, including absorption, distribution, metabolism, and elimination. The effect of the drug is often related to its concentration in the plasma and is calculated using the maximum drug effect and the plasma concentration that generates 50 percent of the maximal effect.
For a bolus drug dose with a half-life of around 3 hours and a C50 of one ng/mL, the peak plasma concentration reaches 64 ng/mL at 3 hours. After 24 hours, the observed drug plasma concentration drops to less than 1% of its peak level, which is half the C50 value. This indicates that ACE is still inhibited by 33%, meaning that the drug's effect on ACE inhibition remains significant even when the drug concentration has decreased. When the concentration exceeds the C80 value, the change in effect becomes insignificant regardless of concentration fluctuations, rendering the curve nearly flat. If the concentration falls between the C80 and C20 values, the effect curve closely resembles a straight line, suggesting that the changes in drug concentration within this range have a linear relationship with the drug's effect. Lastly, when the concentration dips below the C20 value, the curves are nearly parallel, indicating that further decreases in concentration have minimal impact on the drug's effect.