Week 5a

PHRM 6202: Biopharmaceutics and Pharmacokinetics - Week 5 Study Notes

Overview of Pharmacokinetics

• Four Key Aspects of Pharmacokinetics:
  • Absorption
  • Distribution
  • Metabolism
  • Elimination
• Impact of Drug Delivery on PK Aspects:
  • Investigate how drug formulation influences absorption and the other pharmacokinetic parameters.

Oral Drug Absorption

• Key Processes in Oral Drug Absorption:
  • Disintegration: Breakdown of capsules and tablets.
  • Dissolution: The process of a substance dissolving, relevant to powders, suspensions, capsules, and tablets.
  • Absorption: Involves all oral dosage forms with a focus on three main rates:
  • Rate of dissolution
  • Rate of elimination
  • Rate of absorption

Factors Influencing Rate of Drug Absorption

• Dissolution Rate:
  • Can be a limiting step for:
  • Drugs with low solubility.
  • Extended-release formulations.
• Permeation Rate:
  • Passive Diffusion and Active Transport are the two primary methods for drug absorption.

Kinetics of Drug Absorption

• Rate of Dissolution:
  • Zero-order Kinetics: Assumed to be constant under certain conditions.
  • Passive Diffusion: Assumed zero-order at steady state.
  • Active Transport Rate Equation:
  • $\frac{dW}{dt} = P A C_d$
  • $\frac{dW}{dt} = K_{max}\frac{C_d}{C + K_m}$

Oral Drug Administration Factors

• Administration Factors:
  • Dose considerations include age, sex, and disease states.
• Drug Absorption Considerations:
  • Disintegration and Dissolution: Influences by factors such as food, gastric pH, pKa of the drug, solubility, lipophilicity, and particle size.
  • Gastrointestinal Permeation: Affected by gastric pH, lipophilicity, food-drug interactions, and drug transport mechanisms.
• Drug in the Hepatic Portal Vein:
  • Impact from hepatic metabolism, CYP450 enzymes, drug-drug interactions, and plasma protein binding.

Absorption Kinetics and Rate Models

• Absorption Kinetics with First-order Assumption:
  • The rate of absorption $$\frac{dX_a