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]

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moxidectin pour-on formulation (0.5 mg/kg) administered topically to cattle results in zero meat and milk withdrawal times.[1]
In goats, topical application of moxidectin at 0.5 mg/kg was used; milk residues were not detected at 7 days, supporting a milk withdrawal interval of 1 day.[1]
For subcutaneous administration in cattle, moxidectin was given at 0.2 mg/kg body weight; tissue residues in fat, liver, kidney, and muscle were measured post-administration, with injection site and back fat concentrations of 1,178 and 141 μg/kg respectively at 49 days.[1]
In sheep, oral formulation of moxidectin at 0.2 mg/kg is approved with a 14-day meat withdrawal time (France and United Kingdom).[1]
Goat farmers have administered moxidectin orally at the labeled pour-on dose (0.5 mg/kg) for cattle, but actual doses used range from 0.8 to 1.6 mg/kg.[1]

Absorption, Distribution and Excretion
Moxicillin exhibits unrestricted penetration within the parasite because it is a very weak substrate of P-glycoprotein, which is crucial for reducing gastrointestinal absorption of lipophilic compounds and increasing bile, intestinal, and renal secretion. Following oral administration of moxicillin, the maximum plasma concentration was 70.4 mg/kg after 0.37 days, with an AUC of 363.6 mcg/day/ml. Notably, co-administration with lipids improves oral bioavailability. Approximately 2% of the dose is excreted unchanged in feces within 72 hours after oral administration of moxicillin. Renal excretion is negligible. Compared to ivermectin, moxicillin has a larger volume of distribution and mean residence time. The reported volume of distribution for moxicillin is 1.2 L/kg. The apparent clearance of moxicillin is 3.5 L/h.

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Metabolism/Metabolites
Enzymatic modifications of moxicillin in humans and nematodes have been reported. Moxicillin is primarily metabolized via cytochrome CYP3A and CYP2B to produce C29-30- and C14-monohydroxymethyl derivatives. The metabolism of moxicillin is considered to contribute little to its elimination. Other metabolites include an O-demethyl-dihydroxy metabolite. The metabolism of moxicillin is not significant because the main residues in fat, liver, kidneys, and muscle are unmetabolized moxicillin.

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Biological Half-Life
The terminal half-life of moxicillin is 20.2 days.

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Oral bioavailability of moxidectin is 2.7 times lower in goats than in sheep, and half-life in goats is 1.8 times shorter than in sheep.[1]
In cattle, after subcutaneous administration (0.2 mg/kg), half-lives for total residue of moxidectin in fat, liver, kidney, and muscle ranged from 9.0 to 12.2 days.[1]
At 49 days post-subcutaneous administration in cattle, injection site concentration was 1,178 μg/kg, back fat 141 μg/kg, liver and kidney less than 11 μg/kg.[1]
European maximum residue concentrations for moxidectin are 200 μg/kg in fat, 20 μg/kg in kidney, and 20 μg/kg in liver.[1]
FDA tolerances for parent moxidectin in cattle are 50 μg/kg in muscle and 200 μg/kg in liver.[1]
In sheep and cattle, moxidectin has a longer mean residence time than ivermectin when given orally or subcutaneously, possibly related to greater persistence once absorbed systemically.[1]
For oral administration in goats, based on EU sheep data (0.2 mg/kg, 14-day meat withdrawal), an effective residue half-life (ERH) of 3 days is estimated for moxidectin.[1]
Topical application of moxidectin at the label dose (0.5 mg/kg) in cattle has zero meat and milk withdrawal times.[1]

Effects During Pregnancy and Lactation
◉ Overview of Use During Lactation
There is currently no information regarding the clinical use of moxicillin during lactation. However, the drug concentration in breast milk appears to be very low, and no adverse effects are expected on breastfed infants. Although the package insert recommends discontinuing breastfeeding for 7 days after administration, this appears unnecessary; however, discontinuing breastfeeding for 1 day can reduce the infant's drug exposure by 40%. Until more data are available, moxicillin should be used with caution during lactation, especially when breastfeeding newborns or premature infants.
◉ Effects on Breastfed Infants
No published information found as of the revision date.
◉ Effects on Lactation and Breast Milk
No published information found as of the revision date.

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Protein Binding
The pharmacokinetic properties of this drug in humans are unknown.

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No overt toxicity data reported; however, tissue residue tolerances are established for food safety. For cattle, FDA tolerances for parent moxidectin are 50 μg/kg in muscle and 200 μg/kg in liver.[1] European maximum residue concentrations (MRLs) are 200 μg/kg in fat, 20 μg/kg in kidney, and 20 μg/kg in liver.[1] Injection site residues were high (1,178 μg/kg) at 49 days post-subcutaneous administration in cattle.[1]

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

[2]. Moxidectin, From Wikipedia

Moxixetine is a potent, broad-spectrum endoparasitic agent (an antiparasitic drug effective against both internal and external parasites), also effective against nematodes, insects, and mites. It was initially used in cattle and subsequently approved for use in other animals. It is a semi-synthetic methoxyoxime derivative of nelmadetine, a 16-membered pentacyclic lactone belonging to the milbemycin class. Moxixetine differs from nelmadetine in that it lacks the disaccharide moiety at carbon 13, has a substituted olefin side chain at carbon 25, and a unique methoxyoxime moiety at carbon 23. Due to these structural changes, moxixetine is classified as a second-generation macrolide. Moxixetine was developed by Medicines Development for Global Health and approved by the U.S. Food and Drug Administration (FDA) on June 13, 2018. Moxicritin is a macrolide compound derived from Streptomyces cyanogriseus with antiparasitic activity. After administration, moxicritin binds to glutamate-gated chloride channels (GluCl), γ-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 are in a hyperpolarized or depolarized state, leading to muscle paralysis. Moxicritin reduces the motility and reproductive capacity of the parasite, decreases the secretion of its immunomodulatory proteins, and inhibits the release of microfilariae. See also: Moxicritin (note moved to).

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Indications
Moxicritin is indicated for the treatment of onchocerciasis (also known as river blindness) in patients aged 12 years and older. River blindness is caused by a parasite called Onchocerca volvulus, manifesting as severe itching, disfiguring skin lesions, and visual impairment caused by the larvae. Onchocerca volvulus is primarily transmitted between humans by black flies that breed in the fast currents of sub-Saharan Africa, Yemen, and South and Central America. Larvae released by the adult worms invade the skin and eyes, causing severe symptoms there.
FDA Label

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Mechanism of Action
Moxicillin selectively binds to the parasite's GABA-A and glutamate-gated chloride channels, which are crucial for the function of nerve and muscle cells in invertebrates. It is active against the parasite but does not kill it. Once bound, moxicillin increases channel permeability, leading to chloride ion influx, ultimately causing flaccid paralysis of the parasite.

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moxidectin is approved as a pour-on formulation (0.5 mg/kg) in cattle with zero meat and milk withdrawal times.[1] However, extralabel use (e.g., oral administration in goats) requires extended withdrawal intervals. FARAD recommends a meat withdrawal interval (WDI) of 23 days for goats given oral moxidectin pour-on at 0.8-1.6 mg/kg, and a milk and meat WDI of 1 day for topical application in goats.[1] Caution should be exercised when using this drug in an extralabel manner, especially when administering the pour-on formulation orally to goats, because of its greater persistence once absorbed systemically.[1] It is also stressed that irrespective of the route of administration, moxidectin has a longer mean residence time than ivermectin in sheep and cattle when given orally or subcutaneously.[1]

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.)