Lecture 4 — Half-Life, Elimination, and Bioavailability
1. Elimination-rate constant and half-life
• The elimination-rate constant (ke) can be calculated from the slope of the declining part of the concentration–time curve.
• Half-life (t½) is the time required for 50% of the remaining drug to be eliminated in the first-order elimination examples used in the lecture.
• A faster elimination rate corresponds to a shorter half-life.
Example: half-life of 5 hours
The percentage removed in each half-life is the same, but the absolute amount removed gets smaller. The lecture also gives a separate example starting with 200 mg and halving every 4 hours.
2. The five-half-life rule
The lecture emphasizes that after approximately five half-lives, about 97% of the drug has been eliminated in the described model.
This is important for:
• Estimating when a drug is mostly cleared.
• Understanding washout when switching medications, where a washout is clinically required.
• Estimating the time to steady state during repeated dosing: approximately five half-lives.
• Understanding why half-life helps determine dosing frequency.
Steady state: the amount of drug entering the body equals the amount eliminated over the same period.
*The lecture describes a five-half-life interval when changing drugs; actual switching instructions depend on the medications and clinical situation and should not be inferred from this study rule alone.*
3. Bioavailability (F)
Bioavailability is the fraction of an administered dose reaching systemic circulation as intact drug.
• Intravenous administration: F = 1 (100%), because the drug enters systemic circulation directly.
• Other routes: F may be lower because of incomplete absorption or metabolism before the drug reaches systemic circulation.
Bioavailability depends especially on:
1. Route of administration.
2. Drug formulation (e.g., solution, capsule, tablet).
Why bioavailability may be reduced
• Absorption barriers: the drug must cross tissues before reaching blood.
• Presystemic/first-pass metabolism: some drug is metabolized before entering systemic circulation.
4. Examples from the lecture
These are the lecture’s formulation examples, not interchangeable product specifications for every available formulation.
5. Absolute versus relative bioavailability
For absolute bioavailability, the lecture specifies that complete concentration–time profiles are needed for the IV and non-IV routes to calculate their AUCs.
