Ivermectin is an antiparasitic agent widely used to treat infections caused by various parasites. Its pharmacokinetics (PK) involves absorption, distribution, metabolism, and excretion, as detailed below:
1. Absorption
- Route of Administration: Ivermectin is typically administered orally, but it is also available as topical and injectable formulations.
- Bioavailability: Oral bioavailability can range from 60-80%, depending on the formulation and fed vs. fasting state. Taking it with a high-fat meal significantly increases absorption.
- Time to Peak Concentration (Tmax): After oral administration, the peak plasma concentration is reached in about 4-6 hours.
2. Distribution
- Plasma Protein Binding: Ivermectin is highly bound to plasma proteins (~93%).
- Volume of Distribution (Vd): It has a large volume of distribution (Vd > 3 L/kg in humans), indicating extensive tissue distribution.
- Tissue Penetration: It distributes well into tissues but poorly crosses the blood-brain barrier due to the activity of P-glycoprotein (MDR1 efflux pump). This minimizes central nervous system (CNS) effects in humans at therapeutic doses.
3. Metabolism
- Site: Ivermectin is metabolized in the liver.
- Pathways: Primarily via the cytochrome P450 enzyme system (CYP3A4).
- Metabolites: It produces several inactive or minimally active metabolites, which are less potent than the parent drug.
4. Excretion
- Primary Route: Ivermectin is mainly excreted in the feces (~90%) through biliary elimination.
- Urinary Excretion: A small fraction (~1%) is excreted in the urine.
- Half-Life (T½): The terminal elimination half-life ranges between 12-36 hours in humans, depending on individual variability.
5. Special Considerations
- Drug Interactions: Drugs that inhibit or induce CYP3A4 or P-glycoprotein can alter ivermectin’s pharmacokinetics.
- Toxicity: At higher doses or in individuals with genetic variations affecting P-glycoprotein (e.g., MDR1 mutations), ivermectin may accumulate in the CNS, potentially causing neurotoxicity.
Clinical Implications
Ivermectin’s long half-life and extensive tissue distribution make it effective for single-dose treatment in various parasitic infections. The drug’s safety profile is generally excellent when used appropriately.