Ивермектин химические свойства, назначение, производство
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 B1α or as the
dihydroavermectin B1α 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.
Ивермектин препаратная продукция и сырье
сырьё
препарат