# Podgorski - Pharmacokinetics I Flashcards

Rate equation

Rate = Constant * [Drug]^n where n is the kinetic order.

Drug kinetic order definition:

Dependence of rate of a process on the exponent of the drug concentration

Zero order vs. first order

If n=0, [Drug]^0 = 1. The process is not dependent on the drug concentration. The process

proceeds at a constant rate. For drug elimination, a constant amount is lost per unit time.

If n=1, [Drug]^1 = [Drug] and the rate of the process is directly dependent on the drug

concentration. For drug elimination, a constant percent or fraction is lost per unit time.

Processes the follow first order kinetics

hepatic metabolism under ordinary circumstances -therapeutic plasma concentrations below Km

renal excretion under ordinary circumstances -therapeutic plasma concentrations below Km

Examples of zero-order kinetics

Alcohol and aspirin overdose (overwhelms elimination process)

Both are first order at lower concentrations

Phenytoin (Dilantin)

- 100% bioavailable by oral and IV dosing
- liver at almost maximum metabolic capacity when Dilantin is in the therapeutic range

Blood alcohol level considered to be the threshold for a fatal level

Blood alcohol levels of 500 mg/dl are considered to be the threshold for a fatal level.

Graphic test for zero order

Straight-line behavior when concentration data are plotted on a normal (nonlogarithmic) Y axis.

Graphic test for first order

Straight-line behavior when concentration data are plotted on a logarithmic Y axis.

First order behavior for alcohol is seen only when blood levels are below 10 mg/dl.

Between 10 and 100 mg/dl is a transition region between zero and first order.

rate of drug input =

rate of drug input = f(D/T)

Equation for first order disappearance

Amount (time=t) = Amount(start) * e^-kt

Amount at t = starting amount * e^-kt

Significance of t1/2

Time required for amount to decrease to 1/2 of the starting amount.

Each drug has its own characteristic t1/2 value that is determined by the associated elimination process(es)

t1/2 value for a given drug assumes a normal patient with normal liver and kidney function.

t1/2 determines the rate at which blood concentration rises during a constant infusion and falls after administration is stopped.

Factors altering t1/2 value

Changes in volume of distribution – due to age, obesity, etc.

Induction/downregulation of metabolizing enzymes

Drug accumulation in pathologic fluids

Cardiac failure

Kidney failure

Liver failure

Ke=

ke = (0.7)/t1/2

Significance of rate constant: Ke

If t1/2 = 2 day

k = (0.693)/2 day = 0.347/day

This indicates that about 35% of the starting amount will be eliminated in 1 day.

Rate of Drug Output =

Rate of Drug Output = X ke