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Details

Stereochemistry ABSOLUTE
Molecular Formula C37H53NO8
Molecular Weight 639.8186
Optical Activity UNSPECIFIED
Defined Stereocenters 10 / 10
E/Z Centers 2
Charge 0

SHOW SMILES / InChI
Structure of MOXIDECTIN, (23Z)-

SMILES

[H][C@@]12OC\C3=C/C=C/[C@H](C)C\C(C)=C\C[C@@H]4C[C@@H](C[C@]5(C\C(=N\OC)[C@H](C)[C@H](O5)C(\C)=C\C(C)C)O4)OC(=O)[C@H](C=C(C)[C@H]1O)[C@@]23O

InChI

InChIKey=YZBLFMPOMVTDJY-CBYMMZEQSA-N
InChI=1S/C37H53NO8/c1-21(2)14-25(6)33-26(7)31(38-42-8)19-36(46-33)18-29-17-28(45-36)13-12-23(4)15-22(3)10-9-11-27-20-43-34-32(39)24(5)16-30(35(40)44-29)37(27,34)41/h9-12,14,16,21-22,26,28-30,32-34,39,41H,13,15,17-20H2,1-8H3/b10-9+,23-12+,25-14+,27-11+,38-31-/t22-,26-,28+,29-,30-,32+,33+,34+,36-,37+/m0/s1

HIDE SMILES / InChI
Moxidectin is a semi-synthetic methoxime derivative of LL F-2924α, commonly referred as F-alpha or nemadectin F-alpha is a product of fermentation of Streptomyces cyaneogriseus subsp. noncyanogenus, a bacterial organism isolated in 1983 from a sample of sand from Victoria, Australia. Moxidectin is a potent, broad-spectrum endectocide with activity against a wide range of nematodes, insects and acari. The compound acts by binding to ligand-gated chloride channels, more specifically the subtypes that are gamma-aminobutyric (GABA) mediated and glutamate-gated. The consequence of Moxidectin binding and activation is an increased permeability, leading to an influx of chloride ions and flaccid paralysis of the parasite leading to death. The macrocyclic lactones probably act by binding to and opening glutamate-gated chloride channels found only in neurons and myocytes of invertebrates. Because moxidectin is very lipophilic, it becomes highly concentrated in the serum. When the concentration of moxidectin in the serum is high, moxidectin is able to cross the blood-brain barrier. Once it is in the central nervous system, a macrocyclic lactone stimulates the synaptic secretion of the inhibitory neurotransmitter, GABA. By binding at the receptor site, GABA causes influx of chloride ions into neurons, causing the neurons to become hyperpolarised, which in turn, causes diminution in neuronal activity, resulting in sedation and relaxation of the skeletal muscles. Signs displayed by foals with moxidectin toxicity included dyspnoea, depression, ataxia, weakness, coma and seizures. In a Phase 3 study compared the efficacy, safety and tolerability of moxidectin and ivermectin in subjects infected with Onchocerca volvulus, which is the parasite that causes river blindness.

CNS Activity

Curator's Comment: Safety assessments indicated that moxidectin was safe and well tolerated, with a slightly higher incidence of transient, mild, and moderate CNS adverse events (dizziness and somnolence) as compared to placebo.

Originator

Curator's Comment: The first Moxidectin-containing product was an injectable formulation for cattle, approved for commercial use in Argentina in 1989. Additionally, an ongoing collaboration between Wyeth/Fort Dodge Animal Health and the World Health Organization led to the development of an oral formulation of MOX for humans, which is being evaluated in several African countries for prevention of river blindness, a parasitic disease caused by Onchocerca volvulus. # Wyeth Pharmaceuticals

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Target ID: 176472.0
Gene Symbol: unc-49
0.18 nM [Kd]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
MOXIDECTIN

Approved Use

Moxidectin is an anthelmintic indicated for the treatment of onchocerciasis due to Onchocerca volvulus in patients aged 12 years and older.

Launch Date

2018
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
247 ng/mL
36 mg single, oral
dose: 36 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
56.7 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
58.9 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
79.1 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
63.1 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
58.9 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
133 ng/mL
16 mg single, oral
dose: 16 mg
route of administration: oral
experiment type: single
co-administered:
MOXIDECTIN plasma
Homo sapiens
176 ng/mL
24 mg single, oral
dose: 24 mg
route of administration: oral
experiment type: single
co-administered:
MOXIDECTIN plasma
Homo sapiens
247 ng/mL
36 mg single, oral
dose: 36 mg
route of administration: oral
experiment type: single
co-administered:
MOXIDECTIN plasma
Homo sapiens
27.2 ng/mL
4 mg single, oral
dose: 4 mg
route of administration: oral
experiment type: single
co-administered:
MOXIDECTIN plasma
Homo sapiens
56.7 ng/mL
8 mg single, oral
dose: 8 mg
route of administration: oral
experiment type: single
co-administered:
MOXIDECTIN plasma
Homo sapiens
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2613 ng × h/mL
36 mg single, oral
dose: 36 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
632.6 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
3387 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
7885 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: HIGH-FAT
2738 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
3387 ng × h/mL
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
559 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: UNHEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
784 h
8 mg single, oral
dose: 8 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MOXIDECTIN plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Other AEs: Eosinophilia, Pruritus...
Other AEs:
Eosinophilia (74%)
Pruritus (65%)
Musculoskeletal pain (64%)
Headache (58%)
Lymphocytopenia (48%)
Tachycardia (39%)
Postural orthostatic tachycardia syndrome (34%)
Tachycardia (18%)
Rash (37%)
Abdominal pain (31%)
Sources: Page: 3
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Other AEs: Hypotension, Orthostatic hypotension...
Other AEs:
Hypotension (30%)
Orthostatic hypotension (22%)
Pyrexia (27%)
Leukocytosis (25%)
Influenza like illness (23%)
Neutropenia (20%)
Cough (17%)
Lymph node pain (13%)
Dizziness (12%)
Gastroenteritis (15%)
Hyponatremia (12%)
Peripheral swelling (11%)
Eye pain (8%)
Eye pruritus (7%)
Visual impairment (3%)
Eyelid edema (2%)
Conjunctivitis allergic (2%)
Ocular discomfort (2%)
Conjunctival hyperemia (2%)
Lacrimation increased (1%)
Sources: Page: 4
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 5
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 5
Other AEs: Eosinophilia, Lymphocytopenia...
Other AEs:
Eosinophilia (grade 4, 18%)
Lymphocytopenia (grade 3, 23%)
Neutrophils (grade 4, 7%)
Sources: Page: 5
18 mg single, oral
Recommended
Dose: 18 mg
Route: oral
Route: single
Dose: 18 mg
Sources: Page: 1111
healthy, 18-45 years
n = 5
Health Status: healthy
Age Group: 18-45 years
Sex: M
Population Size: 5
Sources: Page: 1111
Other AEs: Somnolence...
Other AEs:
Somnolence (20%)
Sources: Page: 1111
36 mg single, oral
Recommended
Dose: 36 mg
Route: oral
Route: single
Dose: 36 mg
Sources: Page: 1111
healthy, 18-45 years
n = 10
Health Status: healthy
Age Group: 18-45 years
Sex: M
Population Size: 10
Sources: Page: 1111
Other AEs: Somnolence...
Other AEs:
Somnolence (40%)
Sources: Page: 1111
2 mg single, oral
RP2D
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources: Page: 13
unhealthy, adult
n = 44
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 44
Sources: Page: 13
Other AEs: Generalized pruritus, Rash...
Other AEs:
Generalized pruritus (52%)
Rash (41%)
Postural orthostatic tachycardia syndrome (48%)
Orthostatic hypotension (18%)
Lymph node pain (20%)
Sources: Page: 13
4 mg single, oral
RP2D
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources: Page: 13
unhealthy, adult
n = 45
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 45
Sources: Page: 13
Other AEs: Generalized pruritus, Rash...
Other AEs:
Generalized pruritus (80%)
Rash (53%)
Postural orthostatic tachycardia syndrome (31%)
Orthostatic hypotension (29%)
Lymph node pain (36%)
Sources: Page: 13
8 mg single, oral
RP2D
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 13
unhealthy, adult
n = 38
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 38
Sources: Page: 13
Other AEs: Generalized pruritus, Rash...
Other AEs:
Generalized pruritus (88%)
Rash (63%)
Postural orthostatic tachycardia syndrome (63%)
Orthostatic hypotension (60%)
Lymph node pain (63%)
Sources: Page: 13
AEs

AEs

AESignificanceDosePopulation
Tachycardia 18%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Abdominal pain 31%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Postural orthostatic tachycardia syndrome 34%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Rash 37%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Tachycardia 39%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Lymphocytopenia 48%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Headache 58%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Musculoskeletal pain 64%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Pruritus 65%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Eosinophilia 74%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 3
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 3
Lacrimation increased 1%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Peripheral swelling 11%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Dizziness 12%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Hyponatremia 12%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Lymph node pain 13%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Gastroenteritis 15%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Cough 17%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Conjunctival hyperemia 2%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Conjunctivitis allergic 2%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Eyelid edema 2%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Ocular discomfort 2%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Neutropenia 20%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Orthostatic hypotension 22%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Influenza like illness 23%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Leukocytosis 25%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Pyrexia 27%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Visual impairment 3%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Hypotension 30%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Eye pruritus 7%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Eye pain 8%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 4
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 4
Lymphocytopenia grade 3, 23%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 5
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 5
Eosinophilia grade 4, 18%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 5
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 5
Neutrophils grade 4, 7%
8 mg single, oral
Recommended
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 5
unhealthy, 18 - 60 years
n = 978
Health Status: unhealthy
Condition: onchocerciasis
Age Group: 18 - 60 years
Sex: unknown
Population Size: 978
Sources: Page: 5
Somnolence 20%
18 mg single, oral
Recommended
Dose: 18 mg
Route: oral
Route: single
Dose: 18 mg
Sources: Page: 1111
healthy, 18-45 years
n = 5
Health Status: healthy
Age Group: 18-45 years
Sex: M
Population Size: 5
Sources: Page: 1111
Somnolence 40%
36 mg single, oral
Recommended
Dose: 36 mg
Route: oral
Route: single
Dose: 36 mg
Sources: Page: 1111
healthy, 18-45 years
n = 10
Health Status: healthy
Age Group: 18-45 years
Sex: M
Population Size: 10
Sources: Page: 1111
Orthostatic hypotension 18%
2 mg single, oral
RP2D
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources: Page: 13
unhealthy, adult
n = 44
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 44
Sources: Page: 13
Lymph node pain 20%
2 mg single, oral
RP2D
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources: Page: 13
unhealthy, adult
n = 44
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 44
Sources: Page: 13
Rash 41%
2 mg single, oral
RP2D
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources: Page: 13
unhealthy, adult
n = 44
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 44
Sources: Page: 13
Postural orthostatic tachycardia syndrome 48%
2 mg single, oral
RP2D
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources: Page: 13
unhealthy, adult
n = 44
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 44
Sources: Page: 13
Generalized pruritus 52%
2 mg single, oral
RP2D
Dose: 2 mg
Route: oral
Route: single
Dose: 2 mg
Sources: Page: 13
unhealthy, adult
n = 44
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 44
Sources: Page: 13
Orthostatic hypotension 29%
4 mg single, oral
RP2D
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources: Page: 13
unhealthy, adult
n = 45
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 45
Sources: Page: 13
Postural orthostatic tachycardia syndrome 31%
4 mg single, oral
RP2D
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources: Page: 13
unhealthy, adult
n = 45
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 45
Sources: Page: 13
Lymph node pain 36%
4 mg single, oral
RP2D
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources: Page: 13
unhealthy, adult
n = 45
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 45
Sources: Page: 13
Rash 53%
4 mg single, oral
RP2D
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources: Page: 13
unhealthy, adult
n = 45
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 45
Sources: Page: 13
Generalized pruritus 80%
4 mg single, oral
RP2D
Dose: 4 mg
Route: oral
Route: single
Dose: 4 mg
Sources: Page: 13
unhealthy, adult
n = 45
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 45
Sources: Page: 13
Orthostatic hypotension 60%
8 mg single, oral
RP2D
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 13
unhealthy, adult
n = 38
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 38
Sources: Page: 13
Lymph node pain 63%
8 mg single, oral
RP2D
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 13
unhealthy, adult
n = 38
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 38
Sources: Page: 13
Postural orthostatic tachycardia syndrome 63%
8 mg single, oral
RP2D
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 13
unhealthy, adult
n = 38
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 38
Sources: Page: 13
Rash 63%
8 mg single, oral
RP2D
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 13
unhealthy, adult
n = 38
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 38
Sources: Page: 13
Generalized pruritus 88%
8 mg single, oral
RP2D
Dose: 8 mg
Route: oral
Route: single
Dose: 8 mg
Sources: Page: 13
unhealthy, adult
n = 38
Health Status: unhealthy
Condition: onchocerciasis
Age Group: adult
Sex: unknown
Population Size: 38
Sources: Page: 13
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no (co-administration study)
Comment: no in vivo drug-drug interaction between moxidectin and the CYP3A4 substrate, midazolam
Page: 8;12;43;53
weak [IC50 10 uM]
weak [IC50 145 uM]
weak [IC50 459 uM]
weak
weak
yes
no (co-administration study)
Comment: no in vivo drug-drug interaction between moxidectin and the CYP3A4 substrate, midazolam; with
Page: 8;12;43;53
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
limited
limited
limited
major
major
no
no
weak
yes
yes
yes
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans.
1994 Oct 20
A glutamate-gated chloride channel subunit from Haemonchus contortus: expression in a mammalian cell line, ligand binding, and modulation of anthelmintic binding by glutamate.
2002 Mar 15
The antiparasitic moxidectin: safety, tolerability, and pharmacokinetics in humans.
2003 Oct
Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics.
2005
Moxidectin: a review of chemistry, pharmacokinetics and use in horses.
2009 Sep 25
Relative neurotoxicity of ivermectin and moxidectin in Mdr1ab (-/-) mice and effects on mammalian GABA(A) channel activity.
2012
Pharmacological characterization of the Haemonchus contortus GABA-gated chloride channel, Hco-UNC-49: modulation by macrocyclic lactone anthelmintics and a receptor for piperazine.
2012 Apr 30
Moxidectin and the avermectins: Consanguinity but not identity.
2012 Dec
Moxidectin has a lower neurotoxic potential but comparable brain penetration in P-glycoprotein-deficient CF-1 mice compared to ivermectin.
2013 Jun
The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the Phase II clinical trial data.
2015 Mar 19
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: Moxidectin is safe and well tolerated in humans after single, oral doses of 3 mg to 36 mg.
Unknown
Route of Administration: Unknown
In Vitro Use Guide
Curator's Comment: Modulation of Hco-UNC-49 (Haemonchus contortus GABA-gated chloride channel) by moxidectin was tested to determine the effect of these molecules on the Hco-UNC-49 channel. Moxidectin alone does not produce currents at the concentration 10 uM. However, during co-application of moxidectin (10 uM) with 50 uM of GABA, both the homomeric (Hco-UNC-49B; p<0.05) and heteromeric (Hco-UNC-49B/C; p<0.01) Hco-UNC-49 channels displayed an enhanced response.
Unknown
Name Type Language
MOXIDECTIN, (23Z)-
Common Name English
MILBEMYCIN B, 5-O-DEMETHYL-28-DEOXY-25-(1,3-DIMETHYL-1-BUTENYL)-6,28-EPOXY-23-(METHOXYIMINO)-, (6R,23Z,25S(E))-
Common Name English
MOXIDECTIN FOR VETERINARY USE IMPURITY L [EP IMPURITY]
Common Name English
MOXIDECTIN IMPURITY L
Common Name English
Code System Code Type Description
EPA CompTox
DTXSID00861219
Created by admin on Sat Dec 16 08:26:28 GMT 2023 , Edited by admin on Sat Dec 16 08:26:28 GMT 2023
PRIMARY
CAS
119718-45-5
Created by admin on Sat Dec 16 08:26:28 GMT 2023 , Edited by admin on Sat Dec 16 08:26:28 GMT 2023
PRIMARY
PUBCHEM
16760141
Created by admin on Sat Dec 16 08:26:28 GMT 2023 , Edited by admin on Sat Dec 16 08:26:28 GMT 2023
PRIMARY
FDA UNII
TYC529328W
Created by admin on Sat Dec 16 08:26:28 GMT 2023 , Edited by admin on Sat Dec 16 08:26:28 GMT 2023
PRIMARY