Ивермектин

Описание

Ivermectin is an antiparasitic agent effective in the treatment of onchocerciasis, or "river blindness". Since ivermectin acts to prevent the adult worm from producing microfilariae, it needs to be administered only once or twice a year.

Химические свойства

Crystalline Solid

Подготовка

The synthesis of ivermectin involves the hydrogenation of the naturally occurring avermectin B1 (abamectin) at the double bond linking C-22 and C-23. This results in a mixture of two homologues, 22, 23-dihydroavermectin B1a (H2B1a) and 22, 23-dihydroavermectin B1b (H2 B1b). The a- and b- nomenclature refers to the presence on C-25, of either a secondary butyl side chain or an isopropyl group, respectively. The biological activities of H2B1a and H2B1b are similar. Large-scale separation of the two homologues is not practical, and, hence, ivermectin is marketed as a mixture of H2 B1a (>80%) and H2 B1b (<20%).

Показания

Ivermectin (Mectizan) acts on parasite-specific inhibitory glutamate-gated chloride channels that are phylogenetically related to vertebrate GABA-gated chloride channels. Ivermectin causes hyperpolarization of the parasite cell membrane and muscle paralysis.At higher doses it can potentiate GABA-gated chloride channels. It does not cross the blood-brain barrier and therefore has no paralytic action in mammals, since GABA-regulated transmission occurs only in the central nervous system (CNS). Ivermectin is administered by the oral and subcutaneous routes. It is rapidly absorbed. Most of the drug is excreted unaltered in the feces. The half-life is approximately 12 hours.

Антимикробная активность

It is also active against O. volvulus and other filarial worms, but the effect is chiefly directed against the larval forms (microfilariae). Uniquely among anthelmintic agents it exhibits activity against some ectoparasites, including Sarcoptes scabiei.

Биологическая активность

Positive allosteric modulator of the α 7 neuronal nicotinic acetylcholine receptor and the purinergic P2X 4 receptor. Antihelmintic. Also modulates glutamate- and GABA-activated chloride channels. Potentiates glycine-gated currents at low concentrations (30 nM).

Клиническое использование

Onchocerciasis
Non-disseminated strongyloidiasis
Lymphatic filariasis (in combination with albendazole)
Scabies
If the patient is harboring Asc. lumbricoides, the worms will be passed in the feces. Head lice will also be killed, which is very much welcomed by the treated patients. Ivermectin has been widely used in the veterinary field, where use is also made of its effect on ectoparasites.

Побочные эффекты

In the treatment of onchocerciasis mild Mazzotti-type reactions occur, with occasional neurological problems. Although it is highly effective against L. loa, care must be taken to avoid treating patients with high microfilarial counts: there is one report of a patient with a concomitant L. loa infection who died when treated for onchocerciasis. Mild gastrointestinal and nervous system signs may occur following treatment for strongyloidiasis.

Метаболизм

Ivermectin is rapidly absorbed, is bound to a great extent to plasma protein, and is excreted in the urine or feces either unchanged or as the 3′-O-demethyl-22,23-dihydroavermectin B1_α or as the dihydroavermectin B1_α monosaccharide. The absorption of IVM is significantly affected by the presence of alcohol. Administration of IVM as an alcoholic solution may result in as much as a 100% increase in absorption.