Optimum treatment with many drugs depends on achieving a plasma concentration that lies between two specific limits

Drugs with low therapeutic index where the therapeutic dose is close to the toxic dose

Failure of therapeutic response at a dose that is expected to be effective as in patient non-compliance and incomplete drug absorption

In case of multiple drug therapy with the possible occurrence of drug interactions

In presence of organ disease as hepatic or renal disease that adversely affect the pharmacokinetic processes

To diagnose drug toxicity

e.g antihypertensives (blood pressure measurements), oral anticoagulants (prothrombin time) and hypoglycemics (blood sugar), plasma drug concentration is not worth measuring.

"hit and run drugs"

e.g., nortriptyline in small dose inhibits the amine pump and in large dose produces alpha adrenergic blockade

The dose required to quickly reach a specific plasma drug concentration level with a single IV administration

In case of some drugs e.g., digoxin it is necessary to achieve therapeutic levels within hours instead of days to get a rapid response and so we have to give a loading dose (LD)

CL = Vd x Kel .............................. where Kel = elimination rate constant = 0.693/t1/ So equation (2) can be rewritten CL = Vd x 0.693/t1/2 ..........................

The dose required for regular administration to maintain a target plasma level

Css = F.D / Vd. Kel . t .............................. Css = steady state concentration F = bioavailability D = dose Kel = elimination rate constant = 0.693/t1/2 t= dose interval From equations (2) and (4) we can substitute Vd Kel by CL and equation (4) can be written as follows Css = F.D / CL .t ..................................

e.g., 95% of Digoxin

Bioavailability is the fraction of the dose given (F) that reaches the systemic circulation; it has a value between 0 and 1.

Low oral bioavailability denotes

Overview

First order, zero order and non-linear elimination kinetics

It is the time required for the plasma concentration to fall to one half its original value.

As a rule, steady state condition when drug is administered at regular intervals is where the Rate of administration equals to the rate of elimination.

This is attained in 5 half-lives.

Once the drug is stopped elimination is usually complete after 5 half- lives.

It can be determined graphically from the plot of log concentration versus time.

The half - life of a drug has an important role in the selection of dosage interval for maintenance therapy

Two situations illustrate this