Properties
This section outlines the chemical and physical properties of key drug classes monitored in TDM
General Overview of Chemical and Physical Properties in TDM
- Importance: Understanding the chemical and physical properties of drugs is critical for comprehending their ADME processes, mechanism of action, analytical methods, and TDM
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Properties Influencing ADME
- Solubility: Affects absorption and excretion
- Ionization: Impacts absorption, distribution, and renal excretion
- Protein Binding: Influences distribution and free drug concentration
- Partition Coefficient (Log P): Affects membrane permeability and distribution
Drug Classes and Properties
Aminoglycosides (e.g., Gentamicin)
- Definition: Antibiotics used to treat bacterial infections
- Chemical Structure: Amino-modified glycosides (sugars)
- Molecular Weight: 400-600 Da
- Solubility: Highly water-soluble due to multiple polar amino and hydroxyl groups
- Ionization: Polycationic at physiological pH
- Protein Binding: Low protein binding (< 30%)
- Pharmacokinetic Implications: Poor oral absorption, limited distribution, renal excretion
- Analytical Methods: Immunoassays, chromatography, mass spectrometry
Cardioactive Drugs (e.g., Digoxin)
- Definition: Used to treat heart failure and arrhythmias
- Chemical Structure: Steroid nucleus linked to a lactone ring and sugar molecules
- Molecular Weight: Approximately 780 g/mol
- Solubility: Slightly soluble in water
- Ionization: Variable, depends on functional groups
- Protein Binding: Moderate protein binding (20-30%)
- Pharmacokinetic Implications: Oral bioavailability varies, distributes widely, renal excretion
- Analytical Methods: Immunoassays, chromatography
Anticonvulsants (e.g., Phenobarbital)
- Definition: Used to prevent or control seizures
- Chemical Structure: Barbiturate
- Molecular Weight: Approximately 232 g/mol
- Solubility: Slightly soluble in water
- Ionization: Weakly acidic
- Protein Binding: Moderate protein binding (45-60%)
- Pharmacokinetic Implications: Oral bioavailability, extensive metabolism in the liver, renal excretion (pH-dependent)
- Analytical Methods: Immunoassays, chromatography
Antidepressants (e.g., Lithium)
- Definition: Used to treat depression and mood disorders
- Chemical Structure: Simplest structure in the antidepressents, with only a single charge
- Molecular Weight: Approximately 7 g/mol
- Solubility: Lithium salts soluble in water
- Ionization: Exists as a monovalent cation (\(Li^+\)) in solution
- Protein Binding: Negligible protein binding
- Pharmacokinetic Implications: Rapid and complete oral absorption, distributes throughout total body water, renal excretion
- Analytical Methods: Flame Emission Spectrophotometry (FES), Ion-Selective Electrode (ISE), Atomic Absorption Spectrometry (AAS)
Immunosuppressants (e.g., Tacrolimus)
- Definition: Used to prevent organ rejection and treat autoimmune diseases
- Chemical Structure: Macrolide lactone
- Molecular Weight: Approximately 804 g/mol
- Solubility: Practically insoluble in water
- Ionization: Not applicable
- Protein Binding: Highly protein-bound (approximately 99%)
- Pharmacokinetic Implications: Low and variable oral bioavailability, extensive metabolism in the liver, biliary excretion
- Analytical Methods: Immunoassays, chromatography (LC-MS/MS)
Summary Table of Chemical and Physical Properties
| Drug Class | Solubility | Ionization | Protein Binding | Key Chemical Features |
|---|---|---|---|---|
| Aminoglycosides | Water | Polycationic | Low | Amino sugars, glycosidic bonds |
| Cardioactive Drugs | Variable | Variable | Moderate | Steroid nucleus, lactone ring, sugar |
| Anticonvulsants | Slightly Soluble | Weakly Acidic | Moderate | Barbituric acid ring |
| Antidepressants | Water | Monovalent Cation | Negligible | Single positive charge |
| Immunosuppressants | Insoluble | N/A | High | Macrolide lactone |