1. Quantitative Pharmacokinetics
Pharmacokinetics involves the kinetics of drug absorption, distribution, and elimination.
Disposition=Distribution+Elimination

2. Compartment model
The body is viewed as a system with a number of compartments through which the drug is distributed at certain rates.
This pharmacokinetic model has no physiologic meaning, but can be described schematically or mathematically according to constant rates in the cases of absorption and elimination.

3. One-compartment model
The drug is instantaneously and uniformly distributed.
Compartment ka ke
Elimination
Absorption

4. Two-compartment model
Drugs are absorbed into the central compartment , distributed from the central compartment to the peripheral compartment, and eliminated from the central compartment.

5. Drug Plasma Concentration Curves
In practice it is usually the drug concentration in plasma (Cp) that is measured.
The drug concentration in plasma (Cp) is not equal to the drug concentration in the tissues.
Changes in the plasma concentration quantitatively reflect changes in the tissues.

6. Onset: The time it takes for the drug to elicit a therapeutic response
Minimum effective concentration (MEC): a minimum plasma concentration that will produce an effect.
Drug Plasma Concentration Curves
Time-action curve
Onset: The time it takes for the drug to elicit a therapeutic response
Minimum toxic concentration (MTC):a minimum concentration above which toxic effects may be experienced.
Termination
Onset

7. Therapeutic Range: the plasma concentrations between the MTC and the MEC
Drug Plasma Concentration Curves
Time-action curve
Duration of action:
The time between the onset of action and the time when the minimum effective concentration is reached by the declining blood concentrations
Termination
Onset

8. Cmax: maximum concentration
Drug Plasma Concentration Curves
The extent of absorption determines the height of the peak concentration
Time-action curve
toxic concentration
Tmax :the time needed to reach the maximum
Rate of absorption determines the time to the peak concentration
Onset
Termination

9. Area Under the Curve (AUC)
The area under the curve (AUC) refers to the area under a concentration versus time curve for a drug
A measure of the total amount of drug during the time course .
The area is conveniently determined by the “trapezoidal rule”.

10. - quantifies ABSORPTION
Bioavailability
The fraction (F) of the administered dose of a drug that reaches the systemic circulation in an active form.
- quantifies ABSORPTION
Bioavailability is highly dependent on both the route of administration and the drug formulation.

11. Absolute Bioavailability
the amount of drug
that is absorbed by route X
X 100 % F=
the amount of drug that is
absorbed after intravenous administration
X 100 %

12. Relative Bioavailability
Used to compare different formulations of the same medication
AUCtest
AUCreference
Relative Bioavailability F’ =
The same active compound in the same amount just from different manufactures or different batches from the same manufacture will result in equivalent concentrations in plasma and tissues when given to the same patient?

13. Relative Bioavailability
Differences in bioavailability may arise due to variations in disintegration and dissolution rates.
Relative bioavailability is one of the measures used to assess bioequivalence (BE) between two drug products.

14. the same active compound in the same amount
Relative Bioavailability
Chemical equivalence
Bioequivalence
the same active compound in the same amount
the same patient in the same dosage regimen, result in equivalent concentrations of drug in plasma and tissues

15. Rate of Absorption (Rate of Bioavailability)
Bioavailability is sometimes used to indicate both the extent and the rate at which an administered dose reaches the general circulation.
Both the rate of absorption and the extent of absorption can influence the clinical effectiveness of a drug.

16. Bioequivalence: Extent & Rate of Absorption (Extent of absorption)
AUCtest
AUCref
Relative bioavailability F’ =
(Extent of absorption)
Relative bioavailability Cmaxtest
F’’ =
Cmaxref
(Rate of Absorption)
80%<F’ & F”<125%
Two preparations of a drug are considered bioequivalent only when the rate and extent of bioavailability of the drug from them is not significantly different under suitable test conditions.

17. Apparent Volume of Distribution (Vd)
The volume of fluid in which a drug would need to be dissolved to have the same concentration as it does in plasma.
An apparent volume that represents the relationship between the dose of a drug and the resulting plasma concentration of the drug.

18. Vd = Dose (mg)/Cp0 (mg/L)= Litres
Apparent Volume of Distribution
The volume of distribution is normalized to body weight and will then be expressed as units of liters per kilogram.
Cp0
Vd = Dose (mg)/Cp0 (mg/L)= Litres

19. Practice calculation
A dose of analgesic (50mg) is administered i.v. and a blood sample is taken shortly afterwards. The initial concentration of analgesic in the blood sample is 0.85 µg.ml-1.
Calculate the volume of distribution of the
analgesic (in Litres).

20. Model solution V = D/C0 = 50 mg / 0.85 µg.ml-1
Mixed
units!
V = D/C0
= 50 mg / 0.85 µg.ml-1
= 50,000 µg / 0.85 µg.ml-1
= 58,824 ml
= 59 Litres

21. Drug distribution and Body water
Total body water
plasma volume
extracellular
plasma
3 liters 5%
interstitial volume
interstitial volume
15 liters
25%
intracellular volume
intracellular
12 liters
20%
42 liters
70%
Water composition in
60 Kg Body Weight
27 liters 45%

22. (The numbers are only rough approximation)
Table 1. Relationship Between the Extent of Distribution and Vd in a 70 kg normal person
(The numbers are only rough approximation)
Vd, L
% Body Weight
Extent of Distribution 5 7
Only in plasma
5-20
7-28
In extracellular fluids
20-40
28-6
In total body fluids.
>40
>56
In deep tissues; bound to peripheral tissues

23. Drug Clearance
The volume of a biological fluid (generally plasma) from which that drug is removed ("cleared") in the unit of time (min).
Units are in L/hr or L/hr/kg
The clearance of a particular drug is constant in first order kinetics

24. Be not an indicator of how much drug is being removed
Clearance
Rate of elimination
plasma concentration
CL =
Be not an indicator of how much drug is being removed
Represents the theoretical volume of blood which is totally cleared of drug per unit time
A descriptive term used to evaluate efficiency of drug removal from the body

25. Total body clearance is the sum of the individual organ clearances
Clearance is the rate of elimination of a drug by all routes, relative to the concentration of that drug in any biological fluid.
Total body clearance is the sum of the individual organ clearances
CL = CLren + CLhep + CLother

26. Creatinine clearance is 100 ml/min
Drug Clearance
Renal Clearance
The volume of plasma that is totally cleared of a drug in 1 min during passage through the kidneys.
CLrenal= Renal excretion rate = ml/min
Plasma concentration
Creatinine clearance is 100 ml/min
if the CLrenal is 100ml/min, it is filtered only
if the CLrenal is <100ml/min, it is reabsorbed
if the CLrenal is >100ml/min, it is secreted

27. Drug Clearance
Hepatic Clearance
The volume of plasma that is totally cleared of drug in 1 min during passage through the liver.
Most drugs are cleared from the plasma mainly by biotransformation in the liver.
Biliary excretion can also contribute to the hepatic clearance of a drug.

28. Hepatic Clearance Be more difficult to determine than renal clearance.
Drug Clearance
Hepatic Clearance
Be more difficult to determine than renal clearance.
Usually determined by multiplying hepatic blood flow by the arteriovenous drug concentration difference.