PharmSim v2.4

Ivermectin PK/PD & BBB Efflux Simulator

🔬 2D Microvascular & Blood-Brain Barrier Kinetic Visualizer
Plasma Molecule
CNS Molecule
Active P-gp Pump

Blood-Brain Barrier (BBB) Mechanism

In mammals, endothelial cells lining capillary walls express high levels of P-glycoprotein (MDR1 efflux pumps). Even though ivermectin is lipophilic, P-glycoprotein actively transports drug molecules back into systemic circulation, preventing CNS penetration at standard dose levels (0.15–0.20 mg/kg).

📈 Pharmacokinetic Plasma & CNS Profiles
NORMAL THERAPEUTIC
Plasma Cmax
48.2 ng/mL
CNS Conc.
1.4 ng/mL
AUC (0-72h)
1184 ng·h/mL
GluCl Occupancy
94.5%
GABA_A Occupancy
2.1%
🎛️ Dosing Regimen & Physiological Parameters
🧬 Target Receptor Binding Matrix & Clinical Evidence
Ivermectin Pharmacokinetics & Receptor Mechanism Simulator

Receptor Selectivity Comparison

Receptor Type Host Organism Affinity (Kd) Primary Function Clinical Effect
GluCl (Glutamate Chloride) Nematodes / Arthropods ~0.25–1.0 nM Pharyngeal muscle & motoneuron gates Hyperpolarization & Paralysis
GABA_A (γ-Aminobutyric) Mammals (Central Nervous System) ~100–300 nM Inhibitory CNS neurotransmission Protected by BBB efflux

FDA / WHO Approved Indications vs. Toxicity Mechanisms

  • Nobel Prize 2015: Awarded to William C. Campbell and Satoshi Ōmura for discovering Avermectins, revolutionizing treatment for Onchocerciasis (River Blindness) and Lymphatic Filariasis.
  • Anti-Parasitic Safety Margin: GluCl channels in parasites possess ~100x higher affinity for ivermectin than mammalian GABA_A receptors.
  • Neurotoxicity Risk: At high non-indicated doses (>1.0 mg/kg) or in MDR1-deficient individuals, drug concentrations breach the BBB, binding CNS GABA_A receptors and causing ataxia, lethargy, coma, or seizure.
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