pH-Dependent Drug Absorption and Distribution
This interactive module demonstrates gastroenteric absorption and distribution of drugs as a function of pH in different body compartments, focusing on the relationship between logP, pKa, and pH-dependent distribution coefficient (logD).
Drug Properties
Weak Base
2.0
9.5
75
pH Environments
1.5
7.4
7.0
7.2
6.0
Calculations
logD Values
Stomach: -
Enteric (Small Intestine): -
Blood: -
Tissue: -
Urine: -
Ionization (%)
Stomach: -%
Enteric (Small Intestine): -%
Blood: -%
Tissue: -%
Urine: -%
Permeability
Gastric Absorption: -
Intestinal Absorption: -
Blood-Brain Barrier: -
Loading interactive chart…
Loading ionization chart…
Key Concepts in pH-Dependent Drug Distribution
logP (Partition Coefficient): The logarithm of the octanol-water partition coefficient for the unionized form of a drug. This represents the intrinsic lipophilicity of the molecule and determines its ability to cross lipid membranes.
pKa (Acid Dissociation Constant): The pH at which 50% of the drug exists in ionized form and 50% in unionized form. For weak acids, lower pKa means stronger acid; for weak bases, higher pKa means stronger base.
logD (Distribution Coefficient): The pH-dependent distribution coefficient that accounts for both ionized and unionized forms of the drug at a specific pH. This is what actually determines drug behavior in biological systems.
Henderson-Hasselbalch Equations
For weak acids: - logD = logP + log(1/(1 + 10^(pH - pKa))) - % Ionized = 100 × 10^(pH - pKa) / (1 + 10^(pH - pKa))
For weak bases: - logD = logP + log(1/(1 + 10^(pKa - pH)))
- % Ionized = 100 × 10^(pKa - pH) / (1 + 10^(pKa - pH))
Clinical Implications
Gastric Absorption: Only unionized (lipophilic) forms can cross gastric mucosa. Weak acids are better absorbed in the acidic stomach, while weak bases have poor gastric absorption.
Intestinal Absorption: The slightly alkaline intestinal environment (pH ~6.5-7.5) favors absorption of weak bases over weak acids.
Blood-Brain Barrier: Only highly lipophilic, unionized molecules readily cross. The blood pH of 7.4 significantly affects brain penetration.
Renal Elimination: pH-dependent ionization affects both glomerular filtration and tubular reabsorption, allowing for pH manipulation in poisoning cases.
Physiological pH Values
- Stomach: 1.5-3.5 (fasting), 3.0-5.0 (fed)
- Small intestine: 6.5-7.5
- Blood: 7.35-7.45
- Intracellular: 6.8-7.2
- Urine: 4.5-8.5 (variable)
Test your understanding of pH-dependent drug distribution:
1. Calculate logD for the current drug in blood (pH 7.4):
2. What percentage is ionized in the stomach?
3. Which compartment has the highest logD for this drug?