In cattle, the half- lives for total residue of moxidectin in fat, liver, kidney,and muscle ranged from 9.0 to 12.2 days after SC administration (0.2 mg/kg).17 At 49 days, injection sites and back fat concentrations were 1,178 and 141 μg/kg, respectively, and liver and kidney concentrations were less than 11 μg/kg.[1]

Absorption, Distribution and Excretion
The penetration of moxidectin in the parasite is not restricted as this compound is a very poor substrate of p-glycoprotein, which is vital for the reduction of the uptake of lipophilic compounds from the GI tract and for the increase in biliary, intestinal and renal secretion. After oral administration of moxidectin, the plasma maximal concentration of 70.4 mg/kg was reached after 0.37 day with a reported AUC of 363.6 mcg/day/ml. It is also important to mention that oral bioavailability is enhanced with the co-administration with lipids.
When moxidectin is orally administered, 2% of the dose is eliminated unchanged in the feces within 72 hours. Renal elimination is negligible.
Moxidectin presents a larger volume of distribution and mean residence time when compared to ivermectin. The reported volume of distribution is of 1.2 l/kg.
The apparent clearance of moxidectin is 3.5 L/hour.

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Metabolism / Metabolites
Reports have registered enzymatic modification in humans and in nematodes. In the case of moxidectin, there has been registered C29-30- and C14-mono-hydroxymethyl derivatives mainly by the cytochrome CYP3A and CYP2B. The metabolism of moxidectin is considered to contribute to a small extent to the elimination. Some other metabolites formed are O-demethyl-dihydroxy metabolites. The metabolism of the of moxidectin is not major as the major residue in fat, liver, kidney and muscle is the unchanged moxidectin.

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Biological Half-Life
Moxidectin reporter terminal half-life is 20.2 days.

Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of moxidectin during breastfeeding. However, amounts in breastmilk appear to be low and would not be expected to cause any adverse effects in breastfed infants. Although labeling recommends withholding breastfeeding for 7 days after a dose, this appears to be unnecessary; however, withholding breastfeeding for 1 day would decrease infant exposure by 40%. Until more data become available, moxidectin should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
This pharmacokinetic property in humans is unknown.

[1]. Journal of the American Veterinary Medical Association. 2000,217(5): 668–71.

[2]. Moxidectin, From Wikipedia

Moxidectin is a potent, broad-spectrum endectocide (antiparasitic that is active against endo- and ecto-parasites) with activity against nematodes, insects, and acari. It was first used in cattle followed by an approved use in general animals. It is a semi-synthetic methoxine derivative of nemadectin which is a 16-member pentacyclic lactone of the milbemycin class. Moxidectin differs by the absence of a disaccharide moiety on carbon 13, a substituted olefinic side chain at carbon 25 and a unique methoxime moiety at carbon 23. Due to these modifications, moxidectin is classified as a second generation macrocyclic lactone. Moxidectin was developed by Medicines Development for Global Health and FDA approved in June 13, 2018.
Moxidectin is a macrocyclic lactone derived from Streptomyces cyanogriseus with antiparasitic activity. Upon administration, moxidectin may bind to glutamate-gated chloride channels (GluCl), gamma-aminobutyric acid (GABA) receptors and/or ATP-binding cassette (ABC) transporters expressed on nematode neurons and pharyngeal muscle cells. As a result, neurons or muscle cells remain at either hyperpolarization or depolarization state, thereby resulting in muscle paralysis. Moxidectin reduces the motility and fertility of the parasite and its excretion of immunomodulatory proteins, and inhibits the release of microfilariae.
See also: Moxidectin (annotation moved to).

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Drug Indication
Moxidectin is indicated for the treatment of river blindness, also called onchocerciasis, in patients aged 12 years and older. River blindness is caused by a parasitic worm _Onchocerca volvulus_ and it is manifested as severe itching, disfiguring skin conditions and visual impairment caused by the worm's larvae. The transmission of _Onchocerca volvulus_ is performed person to person by black flies that breed in fast-flowing rivers in sub-Saharan Africa, Yemen and South and Central America. The larvae released by the adult parasite invade skin and eyes where they can produce the severe disease manifestations.
FDA Label

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Mechanism of Action
Moxidectin selectively binds to the parasite's GABA-A and glutamate-gated chloride ion channels which are vital for the function of invertebrate nerve and muscle cells. It presents activity against the parasite but it does not kill him. Once moxidectin is bound, there is an increased permeability leading to an influx of chloride ions and flaccid paralysis of the parasite.

C37H53NO8

639.83

639.377

C, 69.46; H, 8.35; N, 2.19; O, 20.00

113507-06-5

16760141

White to off-white solid powder.

1.2±0.1 g/cm3

790.0±70.0 °C at 760 mmHg

132 °C

431.6±35.7 °C

0.0±6.2 mmHg at 25°C

1.581

8.43

2

9

3

46

1340

10

O1[C@]2([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[C@@]([H])(C([H])([H])[H])C([H])=C([H])C([H])=C3C([H])([H])O[C@]4([H])[C@@]([H])(C(C([H])([H])[H])=C([H])[C@@]([H])(C(=O)O[C@@]([H])(C2([H])[H])C([H])([H])[C@@]21C([H])([H])/C(/[C@]([H])(C([H])([H])[H])[C@@]([H])(/C(/C([H])([H])[H])=C(\[H])/C([H])(C([H])([H])[H])C([H])([H])[H])O2)=N/OC([H])([H])[H])[C@@]43O[H])O[H] |c:7,23,27|

YZBLFMPOMVTDJY-LSGXYNIPSA-N

C[C@@H]\1C/C(=C/C[C@@H]2C[C@@H](C[C@@]3(O2)C/C(=N\OC)/[C@@H]([C@H](O3)/C(=C/C(C)C)/C)C)OC(=O)[C@@H]4C=C([C@H]([C@@H]5[C@]4(/C(=C/C=C1)/CO5)O)O)C)/C

Milbemycin B, 5-O-demethyl-28-deoxy-25-(1,3-dimethyl-1-butenyl)-6,28-epoxy-23-(methoxyimino)-, (6R,23E,25S(E))-

Trade names: Moxidectin; CL301423; Cydectin, Equest, ProHeart, Quest; Milbemectin; milbemycin; Milbemycin B; CL-301423; CL 301423; Moxidectin; Cydectin;

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL ( ~156.29 mM )
H2O : ~1 mg/mL (~1.56 mM )
Ethanol : ~100 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (3.91 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (3.91 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly..

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Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 2.5 mg/mL (3.91 mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)