Herb-Drug Interaction Mechanisms in Pharmacokinetics
Summary
Herb–drug interactions arise when constituents of botanical preparations alter the pharmacokinetic profile of co-administered medications. Key processes include absorption, distribution, metabolism and excretion (ADME), collectively determining drug concentration at its site of action. Many herbal constituents affect drug-metabolising enzymes, notably cytochrome P450 (CYP) isoforms, and drug transporters such as P-glycoprotein. Activation of nuclear receptors, for example the pregnane X receptor, can induce CYP3A4 and transporters, leading to accelerated clearance and reduced efficacy of conventional therapies. Conversely, inhibition of these proteins may elevate systemic exposure and risk toxicity. Gut microbiota and intestinal enzymes also play a crucial part in first-pass metabolism, further complicating interaction profiles. The clinical relevance spans a wide spectrum of therapies, from immunosuppressants and anticoagulants to chemotherapeutic agents. Understanding mechanistic pathways allows for risk assessment, clinical monitoring and informed counselling to safeguard therapeutic outcomes.
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Herb-Drug Interaction Mechanisms in Pharmacokinetics publication trend
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Technical terms
Absorption: Process by which a drug passes from site of administration into systemic circulation.
Distribution: Dispersion of a drug throughout body fluids and tissues.
Metabolism: Enzymatic transformation of a drug, often by cytochrome P450 enzymes, into metabolites.
Excretion: Removal of drugs and metabolites from the body, primarily via renal or biliary routes.
Cytochrome P450 (CYP): Family of liver enzymes that catalyse oxidative drug metabolism.
P-glycoprotein (P-gp): Membrane transporter that pumps drugs out of cells, affecting absorption and excretion.
Induction: Increase in enzyme or transporter expression leading to faster drug clearance.
Inhibition: Decrease in enzyme or transporter activity leading to slower drug clearance.
Pregnane X receptor (PXR): Nuclear receptor that regulates expression of CYP3A4 and various transport proteins.
References
- Clinical relevance of St. John's wort drug interactions revisited. British Journal of Pharmacology (2020).
- Herbal Interaction With Chemotherapeutic Drugs—A Focus on Clinically Significant Findings. Frontiers in Oncology (2019).
- An Overview of the Evidence and Mechanisms of Herb–Drug Interactions. Frontiers in Pharmacology (2012).
- Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance. Life (2020).
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