Mathematical aspect of pharmacokinetics Flashcards
First Order Kinetics
A constant fraction of the drug in the body is eliminated per unit time .The rate of elimination is proportional to the amount of drug in the body .
Majority of drugs are eliminated this way
*Rate of elimination is exponential and decreases exponentially with time .
*Dependent on drug elimination and has a constant T1/2 irrespective of the amount of drug
Kel : Fraction of the drug in the body elimnated per unit time - represented by the slop of the log plasma [] VS time
T1/2 : The time taken for the plasma [] to be reduced by .Usually after 4 T1/2 elimination is 94% (is is independent of the drug [])
Zero order kinetics
A constant amount of drugs that is eliminated per unit time . eg alcohol ,phenytoin, salicyclic acid
>It can be caused by saturation or overload of the receptors by the drug
>Elimination of he drug is linear ,independent of the [] of the drug and has no T1/2
Non-linear Pharmacokinetics / Dose- dependent pharmacokinetics
Causes of non-linear pharmacokinetics :
- Saturation of absorption ,distribution and elimination processes
- Presence of saturable tissue binding
- Presence of saturable plasma -protein binding
Volume of drug distribution
- It is a pharmacokinetics parameter
- Represent the Vd of the compartment in which a given drug would have been uniformly distributed in order to give the observed plasma / blood [] if no elimination occurred
*Drugs that are highly lipid soluble such as digoxin have a high Vd whereas drugs that are lipid insoluble have a low Vd eg neuromuscular blockers
Vd= d(total [] of the drug in the system ) / C ( {} of the drug in the plasma after some time )
Vd can exceed the plasma volume
- Factors affecting Vd
* lipid solubility
* Plasma and tissue and protein binding
* Perfusion of tissues
> decreased Vd ;
- low lipid solubility
- decreased tissue binding
- increased protein binding
> increased Vd :
- High lipid solubility
- increased tissue binding
- decreased plasma protein binding
Clearance ; Pharmacological parameter
- Volume of a plasma that is cleared of a drug per unit time
- Clearance varies with body weight and degree of protein binding
- Total clearance = sum of all the individual clearances
- clearance id more useful then T1/2 because it takes blood flow into consideration
- Clearance is independent of the dose and route of admin
- Rate of elimination = Kel *D({} of the drug in the system )
D= C(concentration of the drug after some time)* Vd
therefore : rate of elimination = Kel CVd
Total clearance = Kel CVd
or
Total clearance = Cl (hepatic )+ Cl (renal)
The pharmacokinetic profile of a drug also depends on route of elimination
- Intravenous injection
* Peak plasma [] of the drug is achieved at 0 time - Oral Dose
* Single oral dose will give a single peak plasma []
* the drug then continuously decrease
* repeated doses result in oscillation in plasma []
Bioavailability (F)
The fraction of the dose of a drug that is absorbed into the general circulation
Area under the curve gives the amount of drug absorbed
AUC is obtained from the plasma [] VS time plot
F= AUC / dose
Clearance =F*dose /AUC
Multiple doses
Steady state
- Clearance values can be used to plan dosage regimes
- Css (steady state)= F*D /Vd *Kel *dosing interval
Steady state is when amount ministered = amount eliminated
Steady states are reached within 4 to 5 T1/2
T1/2 is useful for determine dosing intervals that are within the therapeutic window
Css is proportional to dosage interval and to F/Cl
Intravenous Infusion
- Plasma [] rises until elimination = input
* faster infusions get more drugs on board but does not change the time to achieve a steady state
Plasma drug [] vs time graph
*Cmax gives an rate of absorption
Therapeutic window
Optimal range of plasma []at which most of the patients experience desired range
*drugs with smaller therapeuti window require smaller and more frequent doses or different methods of administration
drugs with slow elimination rates rapidly accumulate to toxic levels ,can choose to give one initial dose following with smaller doses
