Oral Medication Bioavailability

Introduction to Bioavailability

Oral bioavailability is the percentage of a drug absorbed into the systemic circulation after passing through the gut, liver, or lungs following oral administration, which is crucial for determining appropriate dosing regimens and predicting therapeutic effectiveness 1
Understanding oral bioavailability is essential for optimizing drug therapy and ensuring that patients receive appropriate doses to achieve therapeutic effects while minimizing adverse reactions 1

The bioavailability of oral medications is affected by molecular weight, lipophilicity/hydrophilicity balance, pKa and ionization state, and solubility, with larger molecules, poor solubility, and unfavorable ionization states generally having lower bioavailability 2
P-glycoprotein (P-gp) efflux, a cell transporter, can pump drugs back into the intestinal lumen, affecting bioavailability 2, 3
First-pass metabolism can significantly affect bioavailability, with drugs undergoing extensive first-pass metabolism typically having lower bioavailability 1
Physicochemical properties, such as molecular weight, lipophilicity/hydrophilicity balance, pKa, and ionization state at physiological pH, can influence bioavailability 1

The dosage form, particle size, and excipients of oral medications can affect their dissolution rates, disintegration, and stability, with smaller particles generally having better dissolution 2
Release mechanisms, such as immediate vs. controlled-release formulations, can impact bioavailability 3
Formulation factors, including dissolution rate, particle size, and excipients used, can also impact bioavailability 1
Crushing tablets may alter bioavailability, but medications like apixaban, rivaroxaban, and edoxaban can be administered in crushed form without altering bioavailability 3

Gastric emptying time, intestinal transit time, and gastrointestinal pH can affect the bioavailability of oral medications, with food either increasing or decreasing bioavailability depending on the drug 2, 3
Rivaroxaban must be taken with food to increase bioavailability by 39% 3
Proton pump inhibitors can reduce the bioavailability of drugs requiring an acidic environment, such as dabigatran etexilate, which has a bioavailability reduced by 20-40% when taken with pantoprazole 2
Hepatic impairment may increase bioavailability of drugs that undergo extensive first-pass metabolism 1
Genetic variations, such as CYP2D6 polymorphisms, can affect drug metabolism and bioavailability 1
Age-related changes, such as decreased metabolism and hepatic blood flow in geriatric patients, can impact bioavailability 1

Renal function affects the elimination of renally cleared drugs, and hepatic function impacts drugs with high first-pass metabolism 2
Drug interactions, such as P-glycoprotein inhibition/induction, metabolic enzyme inhibition/induction, and changes in gastric pH, can alter bioavailability 2, 3
Disease states, such as gastrointestinal disorders affecting transit time, malabsorption syndromes, and altered pH conditions, can impact bioavailability 2, 3

Fluconazole has a high bioavailability of ~90% 4
Voriconazole has a high bioavailability of >90%, which is not affected by gastric pH but decreases when administered with food 4
Dabigatran etexilate has a low bioavailability of 6-7% in healthy older subjects 2
Rivaroxaban has a bioavailability of ~80% 5
Apixaban has a bioavailability of 45% 5

Administering medications with or without food based on specific drug requirements, and spacing medications that interact at the absorption level, is crucial for optimizing drug therapy 2, 3
Generic substitutions may have different bioavailability profiles, and different formulations of the same drug may not be interchangeable, highlighting the importance of bioequivalence considerations 2, 3
Consider bioavailability when switching between oral and intravenous formulations 1
Be aware of food effects on absorption, such as the decrease in voriconazole absorption with food and the increase in itraconazole capsule absorption with food 4
For drugs with poor bioavailability, consider timing of administration relative to meals and monitor for drug interactions that may affect bioavailability through changes in metabolism or absorption 1