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Biopharmaceutics / Lec: 1
Biopharmaceutics:
Dr . Ghufran Mohammad
is
the
science
that
examines
the
interrelationship of the physicochemical properties of the drug, the dosage
form in which the drug is given, and the route of administration on the
rate and extent of systemic drug absorption.
Thus Biopharmaceutics involves factors that influence:
1. The stability of the drug within the product.
2. The rate of drug release from the product.
3. The rate of dissolution of the drug at the absorption site.
4.The availability of the drug at its site of action (the systemic
absorption of the drug).
The goal of biopharmaceutical studies is to develop a dosage form that
will provide consistent bioavailability at a desirable rate. These studies
must be able to assess the impact of the physical and chemical properties
of the drug, drug stability, and large-scale production of the drug product
on the biologic performance of the drug. Moreover, Biopharmaceutics
considers the properties of the drug and dosage form in a physiologic
environment, the drug's intended therapeutic use, and the route of
administration.
Thus the study of Biopharmaceutics allows the pharmacist to design
drug products rationally to deliver the active drug at a specific rate
and amount into the body to optimize therapeutic effect and to
minimize any adverse effects.
I
Scheme demonstrating the dynamic relationships among the drug, the
product, and pharmacologic effect.
Pharmacokinetics:
The study and characterization of the time course (kinetics) of drug
absorption, distribution and elimination (i.e. metabolism and excretion)
(ADME).
The description of drug distribution and elimination is often termed drug
disposition.
 Absorption: is the process of a substance entering the body.
 Distribution: is the dispersion of substances throughout the fluids
and tissues of the body.
 Metabolism: is the irreversible transformation of parent compounds
into daughter metabolites.
 Excretion: is the elimination of the substances from the body.
Pharmacokinetics is also applied to therapeutic drug monitoring (TDM)
for very potent drugs such as those with a narrow therapeutic range, in
order to optimize efficacy and to prevent any adverse toxicity. For these
drugs, it is necessary to monitor the patient, either by monitoring plasma
drug concentrations (e.g. theophylline) or by monitoring a specific
pharmacodynamic endpoint such as prothrombin clotting time
(e.g. warfarin).
II
Bioavailability: The rate and extent of drug absorption.
Bioavailable dose: The fraction of an administered dose of a
particular drug that reaches the systemic circulation intact.
Plasma level-time curve:
The plasma level-time curve is generated by measuring the drug
concentration in plasma samples taken at various time intervals after a
drug product is administered. The concentration of drug in each plasma
sample is plotted against the corresponding time at which the plasma
sample was removed.
III
Drug Product Performance Parameters:
1.
Minimum
effective
concentration
(MEC):
The
minimum
concentration of drug needed at the receptors to produce the desired
pharmacologic effect.
2. Minimum toxic concentration (MTC): The drug concentration
needed to just produce a toxic effect.
3. Onset time: The time required for the drug to reach the MEC.
4. Duration of action: The difference between the onset time and the
time for the drug to decline back to the MEC
5. The time of peak plasma level: The time of maximum drug
concentration in the plasma and is proportional to the rate of drug
absorption.
6. The peak plasma level: The maximum drug concentration, usually
related to the dose and the rate constants for absorption and elimination of
the drug.
7. Area under the curve: It is related to the amount of drug absorbed
systemically.
Pharmacokinetic Models
Drugs are in a dynamic state within the body as they move between
tissues and fluids, bind with plasma or cellular components, or are
metabolized. The biologic nature of drug distribution and disposition is
complex and such factors must be considered when designing drug
therapy regimens.
The inherent and infinite complexity of these events require the use of
mathematical models and statistics to estimate drug dosing and to predict
the time course of drug efficacy for a given dose.
Pharmacokinetic models are used to:
1. Predict plasma, tissue, and urine drug levels with any dosage regimen.
IV
2. Calculate the optimum dosage regimen for each patient individually.
3. Estimate the possible accumulation of drugs and/or metabolites.
4. Correlate drug concentrations with pharmacologic or toxicologic
activity.
5. Evaluate differences in the rate or extent of availability between
formulations (bioequivalence).
6. Describe how changes in physiology or disease affect the absorption,
distribution, or elimination of the drug.
7. Explain drug interactions.
A very simple and useful tool in pharmacokinetics is compartment
models.
Two parameters are needed to describe model 1: the volume of the
compartment and the elimination rate constant, k. In the case of model 4,
the pharmacokinetic parameters consist of the volumes of compartments
1 and 2 and the rate constants k a, k, k 12, and k 21.
V