莫西克丁
**莫西克丁 (Moxidectin)** 是一種強效的第二代巨環內酯類（阿維菌素/米爾貝黴素亞類）抗寄生蟲藥物，廣泛應用於小動物及大動物獸醫學中。 主要藥理特徵包括： * **廣效性**：對多種體內線蟲（蛔蟲、鉤蟲、鞭蟲、心絲蟲幼蟲）及體外節肢動物（跳蚤、蟎蟲、蝨子、牛皮蠅蛆）均有效。 * **高脂溶性**：莫西克丁的脂溶性約為伊維菌素 (Ivermectin) 的 100 倍。這使其能在組織中廣泛分佈、半衰期延長，並能製成長效緩釋劑型（例如 6 個月注射型心絲蟲預防藥）。 * **ABCB1 (MDR1) 安全性**：雖然帶有 ABCB1-1∆ 基因突變的犬隻對巨環內酯類藥物敏感，但在 FDA 核准的標準標籤劑量下（滴劑與口服心絲蟲預防），莫西克丁對這些品種通常是安全的。然而，若超仿單高劑量使用（例如治療毛囊蟲症），可能會引發嚴重的神經毒性。 本藥物有多種劑型，包括外用滴劑（常與益達胺 imidacloprid 結合使用）、緩釋注射液、口服凝膠及澆潑劑。
作用機制: Moxidectin exerts its antiparasitic effects by disrupting the neurological function of invertebrates: * **Glutamate-Gated Chloride Channels (GluCl)**: Moxidectin binds selectively and with high affinity to GluCl channels present in invertebrate nerve and muscle cells → **increases membrane permeability to chloride ions** → causes cellular hyperpolarization → results in flaccid paralysis and death of the parasite. * **GABA Receptors**: It also enhances the release of gamma-aminobutyric acid (GABA) at presynaptic neurons, further blocking post-synaptic stimulation. **Mammalian Safety**: Mammals do not possess GluCl channels. Furthermore, the **P-glycoprotein (P-gp)** efflux pump at the mammalian blood-brain barrier actively prevents moxidectin from entering the central nervous system, protecting mammalian GABA receptors from exposure.
各物種劑量
- Prevention of heartworm disease, adult fleas, ear mites, hookworms, and roundworms (Advantage Multi) · 10 mg/kg imidacloprid/1 mg/kg moxidectin once a month by topical administration · topical · q30d · For cats 2-5 lb = 0.23 mL; 5.1-9 lb = 0.4 mL; 9.1-18 lb = 0.8 mL.
- Feline Aelurostrongylosis (Aelurostrongylus abstrusus) · One to three topical applications of 1 mg/kg moxidectin (in combination with imidacloprid) · topical · 1-3 applications
- Flea, mite, nematode treatment and heartworm prevention · 10 mg/kg body weight imidacloprid and 1.0 mg/kg body weight moxidectin · topical · monthly · Ongoing for prevention · Apply via spot-on pipette. Severe effects may be seen if applied to cats with adult heartworm disease.
- Flea/tick control and heartworm/nematode prevention (Bravecto Plus) · 280 mg/ml fluralaner and 14 mg/ml moxidectin (volume based on weight) · topical · q12w for flea/tick control, q8w for heartworm prevention · Ongoing · Not for use in kittens <9 weeks or cats <1.2 kg.
- Internal parasites · 0.2 mg/kg [1 mL per 11 lb (1 mL per 5 kg) bodyweight] PO (drench) · PO · single dose
- Gastrointestinal helminthes in Camelids (NWC) · 0.2 mg/kg · PO · single dose · Regimen of choice for camelids.
- Gastrointestinal parasites (Oral Gel) · Dial in the weight of the animal on the syringe · PO · single dose · Horses weighing more than 1250 lb require additional gel from a second syringe.
給藥途徑
禁忌症
- Hypersensitivity to the drug
- Dogs not tested for heartworm infection prior to use
- Sick, debilitated, or underweight dogs (specifically for the 6-month injectable)
- Female dairy cattle of breeding age
- Horses intended for food purposes
- Foals younger than 4 months of age
- Kittens < 9 weeks of age
- Dogs < 7 weeks of age
- Dogs with Class 4 heartworm disease
- Cats < 1.2 kg (for fluralaner combination)
- Breeding males (for fluralaner combination)
不良反應
- Dogs: Lethargy, vomiting, ataxia, anorexia, diarrhea, nervousness, weakness, polydipsia, pruritus
- Dogs (Injectable): Rare but serious reports of anaphylaxis, liver disease, autoimmune hemolytic disease, convulsions
- Cats: Recumbency (rare)
- Horses: Minimal at labeled doses; CNS depression and coma reported in foals at high doses
- Cattle: Minimal to nonexistent at labeled doses
- Transient pruritus at application site
- Erythema at application site
- Hypersalivation (if licked)
- Emesis and haematemesis
- Diarrhoea
- Lethargy
- Pyrexia
- Tachypnoea
- Mydriasis
- Severe systemic reactions in cats with adult heartworm disease
藥物相互作用
- Benzodiazepines · Effects may be potentiated by moxidectin; concurrent use is generally not advised.
- P-glycoprotein Inhibitors (Amiodarone, Carvedilol, Clarithromycin, Cyclosporine, Diltiazem, Erythromycin, Itraconazole, Ketoconazole, Quinidine, Spironolactone, Tamoxifen, Verapamil) · May inhibit the efflux pump at the blood-brain barrier, potentially increasing the risk of moxidectin neurotoxicity, especially in dogs with the ABCB1-1∆ mutation.
- P-glycoprotein substrates · Increased risk of neurological toxicity due to competitive inhibition at the blood-brain barrier · major
- Other macrocyclic lactones · Additive toxicity and increased risk of adverse neurological effects · major
監測
- Heartworm status prior to initiation of therapy
- Fecal egg count reduction testing (FECRT) in horses (target >95% reduction to monitor for resistance)
- Signs of neurotoxicity, especially in herding breeds or animals with low body fat
- Heartworm status (antigen/microfilariae testing) prior to initiating preventative therapy
- Resolution of clinical signs of parasitic infection
- Application site for erythema or pruritus
過量
Moxidectin generally has a wide margin of safety when administered at labeled doses. * **Dogs**: Dosages up to 300X (1120 mcg/kg) demonstrated little to no effects in normal dogs. However, in dogs with the **ABCB1 (MDR1) mutant genotype**, toxicity can be seen at doses as low as 90 mcg/kg. * **Clinical Signs of Toxicity**: Dysorexia, hypersalivation, mydriasis, fasciculations, ataxia, tremors, seizures, vomiting, hyperesthesia, and recumbency/coma. * **Treatment**: Supportive care. **Intravenous fat emulsion (IVFE)** has been successfully used to treat toxicity associated with macrocyclic lactones due to their highly lipid-soluble nature.
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