Lecture 3 — Drug Concentration–Time Profiles and Pharmacokinetic Parameters
1. Why pharmacokinetics matters
Pharmacokinetic monitoring is particularly important for drugs with a narrow therapeutic range, where an insufficient concentration may fail to treat symptoms and an excessive concentration may cause toxicity.
Lecture comparison:
• Ibuprofen is presented as a relatively wide-range example, with the lecture mentioning daily doses of 400–3200 mg.
• Theophylline is presented as a narrow-range example: the lecture gives a blood concentration range of 10–20 μg/mL. Below this, symptom control may be inadequate; above 20 μg/mL, serious toxicity including seizures, arrhythmias, and death is described.
*These are the lecture’s educational examples, not individual dosing or monitoring instructions.*
2. Drug concentration–time profiles
A concentration–time profile shows how the concentration of a drug in blood changes after administration. The lecture plots concentration against time, often with a logarithmic concentration axis (semilogarithmic graph).
Intravenous administration
• A drug given IV enters the blood directly; no absorption across a membrane is needed.
• Blood concentration reaches its maximum almost immediately.
• Concentration subsequently decreases with distribution and elimination.
Extravascular administration (e.g., oral)
• The drug must first be absorbed, so the maximum concentration is delayed.
• Concentration rises to a peak, then falls as elimination becomes dominant.
3. Essential parameters
4. How absorption rate changes the graph
For the same drug and dose, a faster-absorbing formulation generally gives:
• Shorter Tmax
• Higher Cmax
• Quicker onset
A slower-absorbing formulation generally gives a later, lower peak and a more prolonged concentration profile. The lecture notes that AUC can remain similar when the total amount absorbed is similar.
5. What determines the profile’s shape?
Absorption, distribution, metabolism, and excretion all contribute. These processes can occur simultaneously, rather than one strictly after another.
The lecture also notes that slower elimination can keep concentrations higher for longer and can affect peak concentration and its timing.
6. Area under the curve (AUC)
• AUC is the mathematically integrated area beneath the concentration–time curve.
• The lecture names the trapezoidal rule as a common calculation method.
• Two profiles can have different Cmax and Tmax yet still have the same AUC.
• AUC helps compare overall drug exposure and is useful in clearance calculations.
7. Half-life and steady state
• Half-life helps estimate how long a drug remains in the body, dosing frequency, and time to reach steady state.
• Steady state occurs during repeated dosing when the rate entering the body equals the rate leaving it (a plateau).
• The lecture introduces the elimination-rate constant ke in relation to calculating half-life; the numerical relationship is developed further in Lecture 4.
