Pharmacology Absorption and Routes of Administration

Absorption

• Absorption is the movement of a drug from the site of administration to the bloodstream.
• Sites of administration differ and influence the absorption barriers.
• The concentration gradient between the blood and site of administration encourages absorption.

Learning Objectives

• Identify routes of administration requiring absorption.
• Define advantages and disadvantages of oral administration.
• Understand and describe the major physiological factors affecting oral drug absorption.
• Understand and describe the major physiochemical factors affecting oral drug absorption.

Systemic Routes of Administration: Parenteral

• Parenteral administration is outside the gastrointestinal tract.
• Absorption phase following parenteral administration is either avoided or occurs at the site of administration.
• Examples include intravenous, intraarterial, intramuscular, subcutaneous, intrathecal, transdermal, and intranasal.

Systemic Routes of Administration: Enteral

• Enteral administration is inside the gastrointestinal tract.
• After oral administration, absorption occurs throughout the intestinal tract.
• The small intestine (especially the jejunum) is the major site of absorption.
• Examples include buccal, sublingual, oral (PO), and rectal.

Routes of Administration Requiring Absorption

• Some routes of administration do not require absorption (e.g., intravenous, intraarterial, intrathecal).
• Other routes require absorption. Examples include intramuscular, subcutaneous, oral, buccal, sublingual, transdermal, and intranasal.

Oral Absorption

• Oral route advantages: convenient and palatable dosage forms, less expensive than parenteral formulations, and administration in outpatient settings.
• Oral route disadvantages: can be inefficient due to multiple barriers to systemic circulation, potential significant local side effects, and variable absorption altering pharmacokinetic profiles.

Sites of Absorption after Oral Administration

• Stomach: pH 1-3, length 0.3m, transit time 0.5 hr, surface area 0.2m².
• Duodenum: pH 5.8-6.5, length 0.3m, transit time <0.1 hr, surface area 0.02m².
• Jejunum: pH 6-8, length 2.5m, transit time 2-3 hr, surface area ~200m².
• Ileum: pH 7-8, length 3.5m, transit time 1 hr, surface area ~3m².
• Large Intestine: pH 5.5-7, length 1.5m, transit time 10-36 hr, surface area ~3m².
• The small intestine, especially the jejunum, is the major site of absorption due to a higher surface area, permeability, and blood flow.

Oral Bioavailability

• Oral bioavailability (F) is the fraction of a drug that reaches the bloodstream after oral administration.
• It represents the amount of drug escaping the intestine and avoiding the first-pass effect.
• F = FF × FG × FH, where FF is the fraction absorbed from the intestine, FG is the fraction escaping the intestine wall, and FH is the fraction escaping the liver.

Factors Affecting Oral Absorption: Physiologic

• Patient factors:
  • Gastric emptying time.
  • Intestinal transit time.
• Drugs:
  • Solubility/dissolution rate.
  • Molecular size.
  • Lipophilicity.

Factors Affecting Oral Absorption: Physiologic - Details

• Gastric Emptying:
  • Accelerators: Liquids, Prokinetic drugs (e.g., metoclopramide).
  • Delays: Food (high fat), Diarrhea, Diabetic gastroparesis, Anticholinergic drugs, Opioids, Constipatation
• Intestinal Transit Time:
  • Accelerators: Diarrhea
  • Delays: Constipation, Anticholinergic drugs, Opioids

Factors Affecting Oral Absorption: Physiochemical

• Solubility/Dissolution: Ability of a drug to dissolve in an aqueous environment, influence by factors like particle size, salt formation.
• Molecule Size: Smaller molecules are generally better absorbed.
• Lipophilicity: Ability to dissolve in lipids – balance is crucial for absorption.
• Dissolution: Rate is calculated by the Noyes-Whitney equation (Dissolution Rate = D * S (Cs – C) / h). Important variables are diffusion coefficient (D), surface area (S), drug solubility (Cs), concentration of drug in the intestines (C), and diffusion layer thickness (h).
• Formulation impacts dissolution rate. Solutions > Capsules > Tablets > Extended-release Tablets

Biopharmaceutical Classification System

• Categorizes drugs into 4 classes based on solubility and permeability.
• Class IV drugs are not typically used in oral formulations.
• Class I: rapid absorption (no apparent rate-limiting step).
• Class II: dissolution is the rate-limiting step.
• Class III: permeability is the rate-limiting step.

This quiz covers the essential concepts of drug absorption and various routes of administration, including oral and parenteral methods. It aims to help you identify different administration routes and understand their physiological and physicochemical factors influencing absorption. Test your knowledge on this crucial aspect of pharmacology!