Introduction to Biopharmaceutics (and Pharmacokinetics)

Introduction to Biopharmaceutics (and Pharmacokinetics) IP 155 Laboratory Daryl E. Kayanan

Drug in dosage form

Pharmacologic effect Degradation 

Liberation  Drug in contact with body’s membranes

Drug particles in body fluids/cavities

Site of action

Dissolution 

Drug in solution

Peripheral Tissues Distribution

Absorption

Blood/Plasma Liver

Free

Bound

Metabolism 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” Solubility Salt forms

Gastric emptying

Dissolution

Diffusion Bioavailability  Absorption Dosage forms

Route of administration

Permeability Bioequivalence

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 (k a) 

•

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 = F  a x F  g x F  h 

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 (AUC 0→t(last) and AUC 0→∞ )