Pharmacokinetics absorption

1. Pharmacokinetics
Pharmacokinetics

2. Pharmacokinetics
Quantitative study of drug movement in, through and out of the
body.
Drug Target
tissue
Absorption Distribution Metabolism Excretion

4. Pharmacokinetic Parameters help determine
• Route of administration,
• Dose,
• Latency of onset,
• Time of peak action,
• Duration of action
• Frequency of administration of a drug.
• All pharmacokinetic processes involve transport of the drug across
biological membranes

5. Transport of drug across membranes
Passive diffusion and filtration Specialized transport
Passive diffusion:
 Most important process of drug
transport
 Movement of drug is concentration
dependent
Carrier transport is of two types:
• Facilitated diffusion
• Active transport

6. • Facilitated diffusion: the carrier moves the poorly diffusible substrate
along its concentration gradient and does not require energy
• Primary active transport: moves the substrate against its concentration
gradient, carrier derives energy by hydrolysing ATP
• Symport: Carrier moves the substrate ‘A’ against concentration gradient,
utilizing energy from downhill movement of another substrate ‘B’ in the
same direction
• Antiport: Carrier moves the substrate ‘A’ against its concentration gradient,
energized by the downhill movement of another substrate ‘B’ in the opposite
direction

7. • Effect of pH:
Facilitated diffusion
Solute carrier (SLC)
Primary active transport
• P-gp
• multidrug resistance
associated protein 2
(MRP 2)
• breast cancer
resistance protein
(BCRP)
Secondary active
transport
• OATP
OCT
• NET, SERT and DAT
• SGLT1 and SGLT2

8. ABSORPTION
• Movement of the drug from its site of administration into the circulation.
• fraction of the administered dose that gets absorbed & rate of absorption
factors affecting absorption
• Passive diffusion,
• Concentration gradients,
• Lipid solubility
• Vascularity of the absorbing surface

9. Various routes of drug administration

10. Bioavailability
• Bioavailability (F) refers to the rate and extent of absorption of a drug from a
dosage form
OR
• fraction of administered dose of a drug that reaches the systemic circulation
in the unchanged form.
• Determination of bioavailability: Bioavailability is determined by comparing
plasma levels of a drug after a particular route of administration with levels
achieved by IV administration
• Bioavailability= AUC by Oral/AUC by I.V

11. Factors that influence bioavailability:
• First-pass hepatic metabolism:
• Solubility of the drug
• Chemical instability
• Nature of the drug formulation:

12. Bioequivalence:
• Two drug formulations are bioequivalent if they show comparable
bioavailability and similar times to peak blood concentrations
• Differences in bioavailability arise due to variations in disintegration and
dissolution rates
• Significance: drugs with low safety margin (digoxin) or where dosage needs
precise control (oral hypoglycaemics, oral anticoagulants)

13. Drug distribution
• The process of translocating drugs from the bloodstream into the tissues is
referred to as distribution
• Extent and pattern of distribution of a drug depends on its:
• Lipid solubility
• Ionization at physiological pH (a function of its pka)
• Extent of binding to plasma and tissue proteins
• Presence of tissue-specific transporters
• Differences in regional blood flow.

14. • How long will be distribution
• Until an equilibrium is established between unbound drug in the plasma and tissue
fluids.
• Subsequently, there is a parallel decline in both due to elimination

15. Apparent volume of distribution (V)
• The apparent volume of distribution (Vd) describes the area of the body to
which drugs are distributed
• this is only an apparent volume of distribution
• Defined as “the volume that would accommodate all the drug in the body, if
the concentration throughout was the same as in plasma”

16. Clinically what do we understand by Vd
• Drug Extensively bound to plasma proteins are largely restricted to the
vascular compartment and have low Vd
• Large value of Vd indicates that larger quantity of drug is present in
extravascular tissue
• Diseases e.g. congestive heart failure, uraemia, cirrhosis of liver, etc. can
alter the Vd of many drugs by altering distribution of body water,
permeability of membranes, binding proteins, metabolites that displace the
drug from binding sites

17. Redistribution
Penetration into brain and CSF :
• Only lipid-soluble drugs, therefore, are able to penetrate and have
action on the central nervous system.
• Efflux transporters like P-gp and anion transporter (OATP) present in
brain and choroidal vessels extrude many drugs that enter brain.
• Inflammation of meninges or brain increases permeability of these
barriers
• Enzymatic BBB: Monoamine oxidase (MAO), cholinesterase etc.
enzymes are present in the capillary walls. Inhibit catecholamine, 5-
HT, acetylcholine, etc. to enter brain in the active form
• Passage across placenta

18. Plasma protein binding:
• Acidic drugs generally bind to plasma albumin and basic drugs to α1 acid
glycoprotein.
• Highly plasma protein bound drugs are largely restricted to the vascular
compartment & have low volumes of distribution.
• Bound fraction is not available for action, acting as temporary storage of the
drug
• High degree of protein binding generally makes the drug long acting,
because bound fraction is not available for metabolism or excretion
• One drug can bind to many sites on the albumin molecule & more than one
drug can bind to the same site. This can give rise to displacement
interactions among drugs bound to the same site(s)

19. • Insight into drug binding to protein binding