Kinetics of elimination and Volume of distribution Flashcards
Volume of distribution (Vd) definition
Apparent volume that would accommodate all the drug in the body in a concentration the same as present in plasma.
Volume of distribution (Vd) equation
Vd = M (dose of the drug adminstered) / C (plasma concentration)
Significance of volume of distribution
1) Drugs highly bound to plasma proteins have small Vd = plasma volume
2) Drugs highly bound to tissue proteins have large Vd = total body water
3) Abnormal accumulation of body fluids as edema may increase Vd of water soluble drugs
4) Useful to calculate loading dose which is the initial large dose to reach a target therapeutic concentration (C).
When to use haemodyalysis when there is toxicity?
For drugs with small volume of distribution because high volume of distribution of a drug means it is bound to tissue proteins and not present in the blood
Loading dose definition
Dose needed to reach certain concentration of the drug in plasma
High volume of distribution means that the drug distributes …
Intracellular
Low volume of distribution means that the drug distributes
intravascular
Loading dose equation
Loading dose = Vd x C (target theraputic concentration) / F (Bioavailability in case of oral drug)
Drug elimination is the ……… and ………..
metabolic inactivation …… excretion
Clearance definition
The clearance (CL) of a drug is the theoretical volume of plasma from which the drug is completely removed in a unit time
Clearance calculation
CL= Rate of Elimination / Plasma Concentration
The rate of elimination can be ……. or ……
First order kinetics
Zero order kinetics
First order kinetics definition
A constant fraction or percentage of the drug present in the body is eliminated in unit time.
Zero order kinetics
Constant amount of the drug is eliminated in unit time
In first order kinetics, The rate of elimination is ……….. to the drug concentration
directly proportional
In zero order kinetics, The rate of elimination ……….. irrespective of drug concentration
remains constant
In first order kinetics, the T half-life is ….
CONSTANT
In zero order kinetics, the T Half-life ….
INCREASES WITH THE DRUG CONCENTRATION
In first order kinetics, the clearance of the drug
remains constant
In zero order kinetics, the clearance of the drug
decreases as the concentration of the drug increases
might lead to toxicity
First order kinetics drug examples
- Most of drugs which do not saturate the elimination processes (transporters, enzymes, blood flow, etc.) over the therapeutic concentration range
- Phenytoin, asprin and ethanol in small doses
Zeroorder kinetics drug examples
Phenytoin, asprin and ethanol in large doses
Due to saturation of enzymes and transporters.
Plasma half life (t1/2) definition
The Plasma half-life (t1/2) of a drug is the time taken for its plasma concentration to be reduced to half of its original value.
After 4 T-half-lives, ……% of the drug is eliminated
94
Plasma half-life calculation
T(1/2) = (0.693 x Vd) / CL
Drugs with low T-half life could be administered by 2 ways:
1) To take the dose after the time finishes
2) Administer the dose through an IV drip /infusion
Significance of T(1/2) life:
1) Determination of the dosing interval (t)
2) Calculation of the maintenance dose
3) Determination of the time needed to reach a steady state concentration “Css”
Maintenance dose definition
Required dose to maintain steady concentration of drug
Most drugs are taken after the T1/2 life why?
To ensure continuous concentration with minimal fluctuations
Steady state concentration definition
The plasma concentration of the drug at which the rate of adminstration equals the rate of elimination
