PK/PD Lab
Bend the curve
One interactive model, every core concept: change the dose, the interval, and the half-life, and watch accumulation, steady state, and the loading-dose shortcut respond. Axes are relative on purpose: this teaches shapes, not any single drug’s numbers.
- Time to steady state
- ~40 h
- Accumulation factor
- ×1.5
- SS peak : trough
- 3.1 : 1.1
- Half-lives per interval
- 1.5
Watch the staircase: each dose adds to what remains of the last, and the curve levels out where input balances elimination, after about five half-lives, whatever the dose. A bigger dose raises the plateau; it does not arrive there any sooner.
The concepts behind the curve
Half-life runs the clock
Half-life sets three clocks at once: how fast a drug leaves, how long a missed dose stays missed, and how long steady state takes to arrive (about five half-lives, always). Amiodarone's weeks-long half-life is why its interactions creep in over a month; venlafaxine's short one is why missed doses bite the same evening.
Steady state is a balance, not a destination
With repeated dosing, each dose stacks on what remains of the last until elimination catches up with input. Raising the dose raises the plateau but never speeds its arrival, only a loading dose does that, by filling the volume of distribution in one step.
Loading vs maintenance
The loading dose answers 'how much drug does the body need to CONTAIN?' (volume of distribution × target concentration). The maintenance dose answers 'how much leaves per interval?' (clearance × concentration). Renal failure changes the second answer, not the first, which is why loading doses often stand while maintenance shrinks.
First-order vs zero-order
Most drugs are first-order: a constant FRACTION leaves per hour, so curves decay exponentially and doubling the dose doubles the level. A few (phenytoin, ethanol, high-dose salicylate) saturate their enzymes and go zero-order: a constant AMOUNT leaves per hour, and a small dose change can produce a huge level change. Narrow-window zero-order drugs are why TDM exists.
Time-dependent vs concentration-dependent killing
Beta-lactams kill by time above MIC. The interval matters more than the peak, hence frequent dosing or extended infusions. Aminoglycosides and quinolones kill by peak. Once-daily aminoglycoside dosing is this principle wearing a schedule.
The therapeutic window
Potency says where the curve sits; the therapeutic index says how much room you have on it. Warfarin, lithium, digoxin, phenytoin, vancomycin: every drug in the TDM module is there because its window is narrow enough that the difference between effect and toxicity is a measurement, not a guess.