Introduction & Biopharmacy
The therapeutic efficacy of a “drug substance” is determined by:
- The intrinsic pharmacological and toxicological properties of the substance (receptor
interaction)
- The extend and rate of delivery of the substance to the site of action. Determined by:
1. The extend and rate of drug release from the dosage form.
2. The site of release of the drug substance from the dosage form.
3. The transport of the drug substance from its site of absorption to the site of
action.
The points 1, 2 and 3 are determined by:
- The physicochemical properties of the drug substance
- The physicochemical properties of the dosage form
- The structure of the dosage form
- The site of drug release from the dosage form
- The route of drug administration
A simplified approach for systemically acting drugs
- Dissolution of the drug, dissolved drugs, in dosage form makes sure the drugs are able to
pass the membrane and to have a therapeutic reaction.
Solute is dispersed in the solvent
Solvent is surrounding the molecules of the solute
Exceptions:
- intravenously injected drugs
- targeted drugs
- not completely dissolved drugs
Locally applied and locally acting drugs
- e.g. dermal or nasal drugs
Distribution: A dynamic equilibrium exists between the concentration of the drug in the
blood plasma and the drug at its site(s) of action
Pharmacokinetics
the study and characterization of the time course of drug liberation, absorption, distribution,
metabolism and elimination (LADME) and it is determined by measuring a plasma profile.
What does the body with the drug after the drug is administered? How good is the drug
absorbed?
, - Liberation: release of drug from dosage form
- Absorption: uptake of the dissolved active substance of the drug in the systemic blood
circulation
Influencing factors: size/charge/lipohilicity/volume for active substance
dissolution/surface/permeability of absorbing membrane/presence metabolizing
enzymes/presence transporters (with active transport)
- Distribution: The distribution/delivery of the drug to the different compartments (e.g.
fluids, organs) in the body
- Metabolism: The chemical conversion (omzetting) of drug substance by the body (often
by enzymes) to different active or inactive substances (metabolites).
- Excretion: The removal of the drug or its metabolites from the body, via urine, bile,
sweat or breath.
Pharmacokinetics after intravenous injection
- Intravenous injection: the complete dose of a dissolved drug is introduced directly (by
injection/infusion) into the blood stream/systemic blood circulation. The bioavailability is
100%. It is generally the fastest way to get a therapeutic effect
- The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse.
- The drug is going to the heart lungs remainder of the body
- Metabolism/excretion of drugs causes a decrease of concentration in blood. They
eliminate the drugs from the blood.
- Distribution of drug over the body: fluids, tissues and organs may have different
concentrations.
- Volume of distribution (Vd) The apparent volume in which the drug is dissolved (L/kg)
after administration
- Clearance (Cl) The blood or plasma volume which is cleared from all drug per unit of time
(ml/min)
The volume of distribution:
- No concentration of drug in organs/fluid/tissues: Vd (17-19) = body volume
- Concentration of drug in organs/fluid/tissues: Vd > body volume
The therapeutic efficacy of a “drug substance” is determined by:
- The intrinsic pharmacological and toxicological properties of the substance (receptor
interaction)
- The extend and rate of delivery of the substance to the site of action. Determined by:
1. The extend and rate of drug release from the dosage form.
2. The site of release of the drug substance from the dosage form.
3. The transport of the drug substance from its site of absorption to the site of
action.
The points 1, 2 and 3 are determined by:
- The physicochemical properties of the drug substance
- The physicochemical properties of the dosage form
- The structure of the dosage form
- The site of drug release from the dosage form
- The route of drug administration
A simplified approach for systemically acting drugs
- Dissolution of the drug, dissolved drugs, in dosage form makes sure the drugs are able to
pass the membrane and to have a therapeutic reaction.
Solute is dispersed in the solvent
Solvent is surrounding the molecules of the solute
Exceptions:
- intravenously injected drugs
- targeted drugs
- not completely dissolved drugs
Locally applied and locally acting drugs
- e.g. dermal or nasal drugs
Distribution: A dynamic equilibrium exists between the concentration of the drug in the
blood plasma and the drug at its site(s) of action
Pharmacokinetics
the study and characterization of the time course of drug liberation, absorption, distribution,
metabolism and elimination (LADME) and it is determined by measuring a plasma profile.
What does the body with the drug after the drug is administered? How good is the drug
absorbed?
, - Liberation: release of drug from dosage form
- Absorption: uptake of the dissolved active substance of the drug in the systemic blood
circulation
Influencing factors: size/charge/lipohilicity/volume for active substance
dissolution/surface/permeability of absorbing membrane/presence metabolizing
enzymes/presence transporters (with active transport)
- Distribution: The distribution/delivery of the drug to the different compartments (e.g.
fluids, organs) in the body
- Metabolism: The chemical conversion (omzetting) of drug substance by the body (often
by enzymes) to different active or inactive substances (metabolites).
- Excretion: The removal of the drug or its metabolites from the body, via urine, bile,
sweat or breath.
Pharmacokinetics after intravenous injection
- Intravenous injection: the complete dose of a dissolved drug is introduced directly (by
injection/infusion) into the blood stream/systemic blood circulation. The bioavailability is
100%. It is generally the fastest way to get a therapeutic effect
- The less bound a drug is, the more efficiently it can traverse cell membranes or diffuse.
- The drug is going to the heart lungs remainder of the body
- Metabolism/excretion of drugs causes a decrease of concentration in blood. They
eliminate the drugs from the blood.
- Distribution of drug over the body: fluids, tissues and organs may have different
concentrations.
- Volume of distribution (Vd) The apparent volume in which the drug is dissolved (L/kg)
after administration
- Clearance (Cl) The blood or plasma volume which is cleared from all drug per unit of time
(ml/min)
The volume of distribution:
- No concentration of drug in organs/fluid/tissues: Vd (17-19) = body volume
- Concentration of drug in organs/fluid/tissues: Vd > body volume
