1. Pharmacokinetics Asst Prof Dr Inam S. Arif

2. Absorption of Drugs (mechanisms & factors controlling)
The transfer of D from site of administration to bloodstream via several mechanisms
Rate & Efficiency
Mechanisms of absorption of drugs from GIT
Passive diffusion
Facilitated diffusion
Active transport
Endocytosis & exocytosis

3. Mechanisms of absorption of drugs from GIT

8. Factors Influencing Absorption
1- Effect of pH
Effective conc. of the permeability form
Ionization constant (pKa)

9. The effect of pH on drug ionisation.
Acidic conditions (low pH, high H+ concentrations) push the equilibrium of acidic drugs towards their un ionised (protonated) form, and basic drugs towards their ionised form.
Basic conditions (high pH) have the opposite effect.

10. Partitioning of acidic and basic drugs across a pH gradient
Partitioning of acidic and basic drugs  across a pH gradient. Only the un ionised forms (DH and D) are able to diffuse across the membrane.
In urine (pH 6), the un ionised acidic drug (DH) can be readily reabsorbed into the plasma, where its ionised form (D−) becomes concentrated, while the ionised basic drug (D+) is trapped within the urine.
Alkalinising the urine would reduce reabsorption of the acid drug and enhance that of the basic drug.

13. Factors Influencing Absorption (cont.)
2- Blood flow
3- Surface area
4- Contact time (diarrhea, parasympathetic, sympathetic, anticholinergic)
5- Expression of P-glycoprotein (expression, resistance)

15. Expression of P-glycoprotein
Multidrug transmembrane transporter ptn
Expression
Function
Multidrug resistance

16. Bioavailability
The fraction of the administered drug that reaches the systemic circulation

17. Factors Influencing Bioavailability:
1st-pass effect
Solubility of D
Chemical instability
Nature of D formulation
Bioequivalence
Therapeutic equivalence

20. Drug Distribution
The process by which a drug reversibly leaves the blood stream and enters interstitium (ECF) and tissues
capillary permeability, T vol., pl ptns binding, & relative lipophilicity
Blood Flow (CO & local BF)
Capillary permeability (capillary structure, chemical nature)e.g. levodopa
Binding to pl ptns & tissues (acrolein metabolite of cyclophosphamide)
lipophilicity

21. Liver and Brain Capillaries

22. Volume of Distribution
Apparent volume of distribution: the fluid volume required to contain the entire drug in the body at the same concentration measured in the plasma
Plasma compartment
ECF
Total body water

23. The Main Body Fluid Compartments

24. Volume of Distribution (cont.)
Apparent volume of distribution (Vd)
Determination of volume of distribution
Plasma half life (t1/2)
Effect of Vd on t1/2

25. Plasma Drug Concentration after Single Injection