Fundamental Hypothesis

Simplest statement

Predictable relationship between plasma (or serum) concentration of drug and its effect

Fancier

Magnitude of desired clinical response and of toxicity are functions of the drug concentration at the site of action and that there is reasonably predictable relationship between plasma (or serum) drug concentration and the concentration at the site of action.

Formula

Dosing rate = Clearance * Css
(mg/hr = L//hr * mg/L)

Css = concentration of drug in plasma at steady state.This works well for IV infusion. For repeated bolus dosing, the OSCILLATIONS in concentration that give rise to peaks and troughs.
Css(ave) = Average drug concentration at steady state. Corresponds to the Css of IV infusion.
On can replace Css in the formula above with Css(ave) as a first approximation
Css(max) = peak concentrations at steady state
Css(min) = trough concentrations at steady state

Simple application

Draw figure of IV infusion to steady state

Input data:

New dose rate = ??

New Rate = Old rate * {Desired Css / Measured Css)
mg/h = mg/h * {(mg/L) / (mg/L)}

60 mg/h = 30 mg/h * {20/10)

First- & Zero-Order Kinetics

Michaelis-Menten plot

One MUST UNDERSTAND the significance of first- and zero-order kinetics

In THIS SHORT TREATMENT of pharmacokinetics, we will deal ONLY with drugs at concentrations where they are eliminated by FIRST ORDER kinetics

Note:
* Upper flat portion is the zero-order portion
* velocity is in mass/time (NOT fraction);
* Drug concentration is in mass/volume

Statement of hypothesis