Pharmacology Of Mebendazole

Indication	For the treatment of Enterobius vermicularis (pinworm), Trichuris trichiura (whipworm), Ascaris lumbricoides (common roundworm), Ancylostoma duodenale (common hookworm), Necator americanus (American hookworm) in single or mixed infections.
Pharmacodynamics	Mebendazole is a (synthetic) broad-spectrum anthelmintic. The principal mode of action for Mebendazole is by its inhibitory effect on tubulin polymerization which results in the loss of cytoplasmic microtubules.
Mechanism of action	Mebendazole causes degenerative alterations in the tegument and intestinal cells of the worm by binding to the colchicine-sensitive site of tubulin, thus inhibiting its polymerization or assembly into microtubules. The loss of the cytoplasmic microtubules leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores. Degenerative changes in the endoplasmic reticulum, the mitochondria of the germinal layer, and the subsequent release of lysosomes result in decreased production of adenosine triphosphate (ATP), which is the energy required for the survival of the helminth. Due to diminished energy production, the parasite is immobilized and eventually dies.
Absorption	Poorly absorbed (approximately 5 to 10%) from gastrointestinal tract. Fatty food increases absorption.
Volume of distribution	Not Available
Protein binding	90-95%
Metabolism	Primarily hepatic. Primary metabolite is 2-amino-5-benzoylbenzimidazole, but also metabolized to inactive hydroxy and hydroxyamino metabolites. All metabolites are devoid of anthelmintic activity.
Route of elimination	In man, approximately 2% of administered mebendazole is excreted in urine and the remainder in the feces as unchanged drug or a primary metabolite.
Half life	2.5 to 5.5 hours (range 2.5 to 9 hours) in patients with normal hepatic function. Approximately 35 hours in patients with impaired hepatic function (cholestasis).
Clearance	Not Available
Toxicity	Acute oral toxicity (LD50): 620 mg/kg [Mouse]. Symptoms of overdose include elevated liver enzymes, headaches, hair loss, low levels of white blood cells (neutropenia), fever, and itching.