CritIC Pharmacokinetics Series: Absorption

Introduction

• Presenter: Jessica
• Series: CritIC, Pharmacokinetics
• Topic: Absorption

Absorption Overview

• Definition: Process of a drug entering systemic circulation.
• Route of Administration:
  • Intravenous (IV): 100% bioavailability (F=100%).
  • Oral: Variable bioavailability (example: Furosemide ~50%).

Pathway of Oral Drug Absorption

1. Stomach:
   • Encounter stomach acid.
2. Intestine:
   • Cross cell membrane to enter portal circulation.
3. Liver:
   • Metabolization occurs before entering systemic circulation (First Pass Effect).

Factors Influencing Absorption

Patient Compliance

• Essential for drug effectiveness but not typically considered in pharmacokinetics.

Stomach Conditions

• pH Level:
  • Low pH degrades unstable drugs (e.g., benzyl penicillin).
• Presence of Food/Other Medications:
  • Calcium/iron decrease absorption of antibiotics like ciprofloxacin and doxycycline.

Intestinal Factors

• Surface Area & Time:
  • Reduced in bariatric surgery patients.
  • Influenced by conditions like diarrhea (decreased time) and ileus (increased time).
• Gut Motility:
  • Affected by medications (e.g., metoclopramide increases, opioids decrease).
• Splanchnic Blood Flow:
  • Decreased flow reduces absorption (e.g., in shock or advanced atherosclerosis).

Drug Properties

• Lipid Solubility:
  • Necessary for crossing lipid-rich cell membranes.
  • Drugs like gentamicin cannot be given orally due to lack of lipid solubility.
• pH Influence:
  • Non-ionized (uncharged) drugs cross membranes more easily.
  • Weak bases absorb in alkaline environments; weak acids in acidic environments.
  • Proton pump inhibitors can alter absorption environments.

Transporters

• P-glycoprotein (PGP):
  • Actively pumps drugs out of intestinal cells, decreasing absorption.
  • Can be induced/inhibited by other drugs.

First Pass Effect

• Definition: Liver metabolizes drug before systemic circulation.
• Example: Nitroglycerin has a significant first-pass effect, requiring alternative administration (e.g., sublingual).

Importance of Bioavailability

• Dosing Adjustments:
  • Example with furosemide: Oral to IV conversion requires considering bioavailability.
• Clinical Relevance:
  • Understanding necessary for proper dosing transitions between oral and IV routes.

Conclusion

• Next Topic: Drug distribution after entering systemic circulation.
• Engagement: Encouragement to like, share, and provide feedback.

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• Note: These notes provide a structured summary of key points from the lecture on drug absorption, relevant for pharmacokinetic studies.