special topics

CLINICAL PHARMACEUTICS

• drug’s movement through the body

• what the body does to (or with) the drug

• achieve efficacy without toxicity

• plasma concentration (Cp) within the ‘therapeutic window’

• Application of Therapeutic Drug Monitoring (TDM)

• individualization of drug therapy

INAPPROPRIATE DOSING

• dosing too high in relation to the patient’s CL- toxicity likely

• dosing too low in relation to the patient’s CL- drug may be ineffective

IMPORTANT PHARMACOKINETIC PARAMETER

• half life

• vd

• clearance

IMPORTANT PHARMACOKINETIC PARAMETER

half life

Time to steady state and the dosing interval

IMPORTANT PHARMACOKINETIC PARAMETER

volume of distribution

Loading dose (double the value of the maintenance dose)

IMPORTANT PHARMACOKINETIC PARAMETER

clearance

maintenance dose

STEADY-STATE CONCENTRATION (CSS)

is only applicable to

first order reactions

STEADY-STATE CONCENTRATION (CSS)

The rate of drug leaving the body is equal to the

rate of drug entering the body.

STEADY-STATE CONCENTRATION (CSS)

For therapeutic purposes, the time for the plasma drug concentration to reach __

more than 95% of the steady-state drug concentration in the plasma is often estimated

Steady-state occurs after

a drug has been given for approximately four to five elimination half-lives

At steady-state, the rate of drug administration

equals the rate of  elimination and plasma concentration - time curves found after each dose should be approximately super imposable.

At steady-state, the rate of drug administration equals the rate of  elimination and plasma concentration - time curves found after each dose should be approximately super imposable.

rate of drug input (infusion rate) = rate of drug output (elimination rate)

STEADY-STATE CONCENTRATION (CSS)

importance

• Increase in Cp and rate of elimination (1st order) until steady-state is reached 

• Rate in = Rate Out 

• Reached in 4 to 5 half-lives 

• dCp/dt = 0

• Important when interpreting drug concentrations in TDM or assessing clinical response

If the elimination will follow zero order not the first order 

• Rate of input > rate of elimination 

• There will be continuous increase in Cp 

• Steady state will not be reached

STEADY-STATE CONCENTRATION (CSS)

is dependent on

1. Volume of distribution (Vd) 

2. Elimination rate constant (k) 

3. Infusion rate (R)

LOADING DOSE (LD)

If immediate effect is needed, a loading dose (LD) must be given

ORAL LOADING DOSE

LD (oral) followed by maintenance dosing

NO LD: ORAL

Similarly, if dosing is started with oral maintenance dosing, it takes four half-lives to approach steady state.

NO LD: CONTINUOUS INFUSION

If dosing is started by continuous infusion of the maintenance dose, it takes four half-llives to approach steady state.

If immediate effect is needed,

a loading dose (LD) must be given

loading dose is administered __

at the start of a dosage regimen to achieve effective Cp rapidly

Loading dose can produce

an initial blood level either slightly higher or lower than Css

Multiple small loading doses or intermittent IV infusion to

prevent Cp from becoming too high

If large doses are given at wider dosage intervals,

wide fluctuations will occur

MAINTENANCE DOSE (MD)

• Dose required to obtain a given steady-state plasma concentration (Css)

• Obtained from Clearance (Cl)

MAINTENANCE DOSE (MD)

is intended to

sustain a certain plasma concentration

MAINTENANCE DOSE (MD)

is administered as

• constant rate infusion

Drugs with longer elimination half-life

(levothyroxine, Oral contraceptives)

MAINTENANCE DOSE (MD)
For missed doses,

• minimal consequences since small fraction of drug is lost

• Take the next dose as soon as patient remembers

• If almost time for next dose, skipped dose should not be taken, follow regular dosing schedule

MAINTENANCE DOSE (MD)

use of controlled release formulations

Improve patient compliance (BID than TID)