Introduction to Biopharmaceutics (and Pharmacokinetics)

IP 155 Laboratory Daryl E. Kayanan

Biopharmaceutics
Drug in dosage form

Pharmacodynamics
Pharmacologic effect

Liberation
Drug in contact with bodys membranes

Degradation

Drug particles in body fluids/cavities

Site of action

Dissolution
Drug in solution

Peripheral Tissues
Distribution

Absorption
Blood/Plasma Liver
Free Bound

Metabolism

Pharmacokinetics

Excretion
Elimination

Kidneys

Biopharmaceutics
Biopharmaceutics is the study of the interrelationships between the physical and chemical properties of the drug, the design and choice of its system of drug delivery, and the expected therapeutic response after its administration to the patient Biopharmaceutics is interrelated with Physical pharmacy Medicinal chemistry Pharmacokinetics Formulation

Biopharmaceutics
Pharmaceutics + Bio interdependence of biological aspects of the living system and the physical-chemical properties that govern the preparation and behavior of the drug Liberation + Absorption
Dissolution

Solubility
Salt forms

Diffusion Bioavailability
Absorption Dosage forms

Gastric emptying

Permeability
Bioequivalence

Route of administration

Pharmacokinetics
Kinetics of drug absorption, distribution, and elimination Deals with the time course of drug in the body (ADME)
Drug at site of absorption Drug is absorbed Drug is distributed to different tissues

Disposition

Drug is metabolized

Elimination

Drug is excreted by the body by different means

Drug concentration-time profile

Characterization of the time course of a drug inside the body
Administration of the same dose of different drugs to the same individual will produce different conc-time profiles. This is because different drugs have different absorption and disposition characteristics Administration of the same dose of a drug to different individuals will produce different conc-time profiles as well the same drug can be absorbed, distributed, and eliminated at different rates in different individuals

Pharmacokinetics
Each process or processes combined is associated with one or more pharmacokinetic parameters describe or determine the rate and/or magnitude of the different processes
Examples Half-life (t1/2)
how long would a drug stay in the body

Absorption rate constant (ka)

Factor that determines how fast can a drug be absorbed at a specific site of action

Clearance
Capability of a drug to be cleared from the bloodstream or by an organ, which may either proceed to elimination or distribution to other tissues

Rates and Orders of the Pharmacokinetic Process

The rate
Instantaneous speed at which a process occurs (ex. Rate of drug absorption = amt absorbed per unit time)

The Rate Constant

Factor that determines the rate of the process

The Order
Determines how the amount of the drug involved will influence the rate of the process

Orders of pharmacokinetic processes

Zero-order process Constant rate constant amount of drug involved in the process C = Co - kt First order process Constant percentage of drug involved rate is proportional to the amount of drug involved in the process ln C = ln Co - kt

Drug Absorption
Definition: Absorption is the rate and extent at which drugs reach the systemic circulation from the site of drug administration

Thus A drug has been absorbed if it has reached the systemic circulation Also Drugs directly administered into the bloodstream are assumed to be 100% absorbed

Drug Absorption
Drugs administered extravascularly would not have 100% absorption. Biopharmaceutics is concerned with the factors affecting drug absorption, as well as factors affecting drug liberation 2 fundamental parameters that govern drug absorption:
Solubility Permeability

Bioavailability (F)
The fraction of drug dose of unchanged drug that reaches the systemic circulation

The rate and extent to which the API is absorbed from the drug product and becomes available at the site of action

F = Fa x Fg x Fh
Fa = fraction of drug absorbed Fg = fraction of drug that escapes gastrointestinal metabolism Fh = fraction that escapes first-pass effect

Bioequivalence
Two drug products (same API) are bioequivalent if after drug administration of the same molar dose, their bioavailabilities are the same and provide similar effects with respect to safety and efficacy. Should apply both in single or multiple administrations Results in vivo reflect the biopharmaceutics of the drug product The goals of generic drugs are to be bioequivalent with the innovator drug

Pharmacokinetic basis of bioequivalence

Based on these 3 parameters: 1. Maximum drug concentration (Cpmax) 2. Time to peak (tmax) 3. AUC (AUC0t(last) and AUC0)