Pharmacokinetics: Multiple Dosage Regimens (I)

What is the aim of multiple dosage regimens?

To maintain plasma drug concentration within the therapeutic window for a prolonged period of time

What is the principle of superposition?

Early doses do not affect the pharmacokinetics of subsequent doses

How can pharmacokinetics after multiple doses can be calculated?

Using data from a single dose

What is the exception of the Principle of Superposition?

--- non-linear pharmacokinetics (the zero-order kinetics for the first step is sometimes OK)

--- enzyme induction

--- enzyme inhibition

--- changing pathophysiology

What are the formulas used for this part are valid for?

The one-compartment situation

Release and absorption either

Do not exist or are sufficiently fast to be considered instantaneous

What is the plasma-tissue distribution like?

Fast so that it can be considered instantaneous 

What is elimination like?

Only time-dependent process

Plasma drug concentration and the rate of elimination are?

Proportional

What is the consequence?

Plasma drug levels will eventually level off, if drug doses are given at equal intervals

Maximum, minimum, and average steady state concentration are

Constant

What is the rate of input equals to at steady state?

Rate of output

What is the minimum steady-state concentration?

The steady state concentration at the end of the dosing interval

If the drug is administered at a fixed dose and a fixed dosage interval?

The average amount of drug in the body will increase then plateau

What will the mean plasma level be?

Will be higher than the peak Cpmax obtained from the initial dose

The dosing interval should be?

shorter than the time for “complete” elimination (< 4-6 half lives)

At steady state, plasma drug levels?

Fluctuate between C max and C min