Pharmacology-1 ll

Riphah International university

Bioavailability:

 Bioavailability is the fraction of administered drug that reaches the systemic

circulation.
IV provides 100% Bioavailability
Oral usually has less than IV
 100 mg of a drug are administered orally, and 70 mg of this drug are absorbed
unchanged, the bioavailability is 0.7, or 70 percent.
 important for calculating drug dosages for non-intravenous routes of
administration
.Determination of bioavailability:
Factors that influence bioavailability:

a. First-pass hepatic metabolism:

 First-pass metabolism limits the efficacy of many drugs when taken orally. For
example, more than 90% of nitro glycerin is cleared during a single passage
through the liver, which is the primary reason why this agent is administered
via the sublingual
b. Solubility of the drug:
 Very hydrophilic drugs are poorly absorbed, their inability to cross the lipid-rich cell membranes
 drugs that are extremely hydrophobic are also poorly absorbed, because they are totally
insoluble in aqueous body fluids
 drug must be largely hydrophobic, yet have some solubility in aqueous solutions.
C. Chemical instability:
 penicillin G, are unstable in the pH of the gastric contents.
 insulin destroyed in the GI tract by degradative enzymes.
d. Nature of the drug formulation:

 Drug absorption may be altered by chemistry of the drug.

 Particle size
 Enteric coating
Drug distribution:
is the process by which drug reversibly leave the blood stream
and enter the extracellular fluids and tissues.
The distribution of drug from plasma to interstitium depends on
following factors:

A. blood flow:
 Blood flow to vessel rich organs higher such as brain, kidney and liver than skeletal muscles,
skin, and viscera.
 Propofol- rapid distribution to CNS produces anesthesia
Capillary permeability:

 Depends on drug nature and capillary structure

 Liver and spleen-discontinuous capillaries through which large plasma
proteins can pass
C. Binding of drugs to plasma proteins and
tissues

1. Binding to plasma proteins: Reversible binding to plasma proteins

sequesters drugs in a no diffusible form and slows their transfer out of the
vascular compartment.
 Plasma albumin is the major drug-binding protein and may act as a drug
reservoir.
 2. Binding to tissue proteins: Numerous drugs accumulate in tissues, leading
to higher concentrations of the drug in tissues than in the extracellular fluids
and blood.
Hydrophobicity:
The chemical nature of a drug strongly influences
its ability to cross cell membranes. Hydrophobic drugs readily move across most biologic
membranes.
 D. Volume of distribution
 The apparent volume of distribution, Vd, can be thought of as the fluid volume that is required
to contain the entire drug in the body at the same concentration measured in the plasma. It is
calculated by dividing the dose that ultimately gets into the systemic circulation by the plasma
concentration at time zero (C0).
Drug clearance through metabolism:

 Once a drug enter the body, elimination begins.

1. Hepatic metabolism
2. Biliary metabolism
3. Urinary excretion

Clearance (CL): estimate the volume of blood from which the drug is cleared per
unit time.
Kinetics of metabolism:

 First-order kinetics:

 Linear kinetics
 Drug metabolism and elimination is directly proportional to concentration of
free drug
2. Zero-order kinetics:

 The enzyme is saturated by a high free-drug concentration, and the rate of

metabolism remains constant over time. This is called zero order kinetics
 the rate of elimination is constant and does not depend on the drug
concentration.
.