Drug interaction at pharmacokinetic level.
Drug interactions at the pharmacokinetic level occur when one drug affects the absorption, distribution, metabolism, or excretion of another drug. These interactions can alter drug concentrations in the bloodstream and their availability at target sites, leading to enhanced or diminished effects and potential toxicity.
Absorption
1.1 Altered Gastric pH
- Some drugs change the gastric pH, affecting the solubility and absorption of other drugs.
- Example: Antacids increase gastric pH, reducing the absorption of certain antifungal drugs like ketoconazole and itraconazole, which require an acidic environment for optimal absorption.
- Other examples: Proton pump inhibitors (PPIs) like omeprazole can decrease calcium carbonate absorption, increasing the risk of osteoporosis.
1.2 Complexation and Chelation
- Some drugs can bind to metal ions, forming insoluble complexes that reduce absorption.
- Example: Tetracyclines and fluoroquinolones form chelates with calcium, magnesium, or iron supplements, decreasing antibiotic effectiveness.
- Clinical advice: Avoid taking these antibiotics with dairy products, antacids, or iron supplements.
1.3 Changes in Gastrointestinal Motility
- Drugs that increase or decrease gut motility can alter absorption rates.
- Example: Metoclopramide increases gastric emptying, which can enhance the absorption of drugs like paracetamol.
- Example: Opioids (e.g., morphine) slow gastric motility, delaying drug absorption.
1.4 Alteration of Intestinal Flora
- Antibiotics can alter gut microbiota, affecting drug metabolism and absorption.
- Example: Broad-spectrum antibiotics reduce gut bacteria responsible for recycling estrogen, decreasing oral contraceptive effectiveness.
- Example: Rifampin induces metabolism of oral contraceptives, increasing pregnancy risk.