A microtubule is composed of polymers of α- and β-tubulin. Mechanism of action As a vermicide,<unk>  causes degenerative alterations in the intestinal cells of the worm by binding to the colchicine-sensitive site of β-tubulin, thus inhibiting its polymerization or assembly into microtubules (it binds much better to the β-tubulin of parasites than that of mammals).<unk>  leads to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depletes their glycogen stores.<unk>  also prevents the formation of spindle fibers needed for cell division, which in turn blocks egg production and development; existing eggs are prevented from hatching. Cell motility, maintenance of cell shape, and intracellular transport are also disrupted. At higher concentrations, it disrupts the helminths' metabolic pathways by inhibiting metabolic enzymes such as malate dehydrogenase and fumarate reductase, with inhibition of the latter leading to less energy produced by the Krebs cycle. Due to diminished ATP production, the parasite is immobilized and eventually dies. Some parasites have evolved some resistance to<unk>  by having a different set of acids constituting β-tubulin, decreasing the binding affinity of<unk> . Some are not vulnerable to<unk>  itself but instead live in symbiosis with Wolbachia. Wolbachia are necessary to the parasitic worms' moulting and population reduction by<unk>  prevents this and kills the adults. Pharmacokinetics Oral absorption of<unk>  varies among species, with 1–5% of the drug being successfully absorbed in humans, 20–30% in rats, and 50% in cattle. The absorption also largely depends on gastric pH. People have varying gastric pHs on empty stomachs, and thus absorption from one person to another can vary wildly when taken without food. Generally, the absorption in the GI tract is poor due to<unk> 's low solubility in water. It is, however, better absorbed than other benzimidazole carbamates. Food stimulates gastric acid secretion, lowering the pH and making<unk>  more soluble and thus more easily absorbed. Oral absorption is especially increased with a fatty meal, as<unk>  dissolves better in lipids, allowing it to cross the lipid barrier created by the mucus surface of the GI tract. To target intestinal parasites,<unk>  is taken on an empty stomach to stay within the gut. Absorption is also affected by how much of the<unk>  is degraded within the small intestine by metabolic enzymes in the villi. General metabolism of<unk>  and its sulfoxides. The pharmacokinetics of<unk>  differ slightly between men and women: women have a lower oral clearance and volume of distribution, while men have a lower serum peak concentration.<unk>  undergoes very fast 1st-pass metabolism in all species, such that the unchanged drug is undetectable in plasma. Most of it is oxidized into<unk>  sulfoxide (also known as ricobendazole and<unk>  oxide) in the liver by cytochrome P450 oxidases (CYPs) and a flavin-containing monooxygenase (FMO), which was discovered later. In humans, the cytochrome P450 oxidases are thought to include CYP3A4 and CYP1A1, while those in the rats are thought to be CYP2C6 and CYP2A1. Oxidation to<unk>  sulfoxide by FMO produces R(+) enantiomers, while oxidation the cytochromes and by some enzymes in the gut epithelium produce S(-). Different species produce the R(+) and S(-) enantiomers in different quantities; humans, dogs, and most other species produce the R(+) enantiomer more (with the human AUC ratio being 80:20). Compared to the S(-) enantiomer, the R(+) has greater pharmacological activity, lasts longer in the bloodstream, is found in higher concentrations in the infected host tissues, and is found in higher concentrations within the parasites themselves. Some<unk>  is also converted to hydroxyalbendazole, mainly by CYP2J2. For systemic parasites,<unk>  acts as a prodrug, while<unk>  sulfoxide reaches systemic circulation and acts as the real antihelminthic.<unk>  sulfoxide is able to cross the blood-brain barrier and enter the cerebrospinal fluid at 43% of plasma concentrations; its ability to enter the central nervous system allows it to treat neurocystocercosis.<unk>  sulfoxide is converted to the inactive<unk>  sulfone by cytochrome P450 oxidases, thought to include CYP3A4 or CYP2C. Other inactive metabolites include: 2-aminosulfone, ω-hydroxysulfone, and β-hydroxysulfone. The major final metabolites that are excreted by humans are: * methyl 5-(propylsulfonyl-1H-benzimidazol-2-yl) carbamate, * methyl 6-hydroxy 5-(n-propylsulfonyl)-1H-benzimidazole-2-yl) carbamate, * methyl 5-(n-propylsulfinyl)-1H-benzimidazole-2-yl) carbamate, * 5-(n-propylsulfonyl)-1H-benzimidazole-2-yl amine, and * 5-(n-propysulfinyl)-1H-benzimidazole-2-yl amine. There are also some minor hydroxylated sulfated or glucuronidated derivatives. No unchanged<unk>  is excreted, as it is metabolized too quickly. In humans, the metabolites are excreted mostly in bile, with only a small amount being excreted in the urine (less than 1%) and feces. In ruminants, 60–70% of the metabolites are excreted in the urine. Like all benzimidazoles,<unk>  has no residual effect, and thus protects poorly against reinfestations.
Albendazole
Flubendazole
Tiabendazole
Mebendazole
Triclabendazole
Praziquantel
Pyrantel
Avermectin