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
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
DescriptionSources: http://www.sciencedirect.com/topics/neuroscience/moxidectinhttp://www.ncbi.nlm.nih.gov/pubmed/24533275 | http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/VeterinaryMedicineAdvisoryCommittee/UCM127124.pdf | http://www.ncbi.nlm.nih.gov/pubmed/19778466 | http://www.ncbi.nlm.nih.gov/pubmed/14517193 | http://www.ncbi.nlm.nih.gov/pubmed/16569295
Sources: http://www.sciencedirect.com/topics/neuroscience/moxidectinhttp://www.ncbi.nlm.nih.gov/pubmed/24533275 | http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/VeterinaryMedicineAdvisoryCommittee/UCM127124.pdf | http://www.ncbi.nlm.nih.gov/pubmed/19778466 | http://www.ncbi.nlm.nih.gov/pubmed/14517193 | http://www.ncbi.nlm.nih.gov/pubmed/16569295
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.
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
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
| 0.18 nM [Kd] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | MOXIDECTIN Approved UseMoxidectin is an anthelmintic indicated for the treatment of onchocerciasis due to Onchocerca volvulus in patients aged 12 years and older. Launch Date2018 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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 Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03012828 |
16 mg single, oral dose: 16 mg route of administration: oral experiment type: single co-administered: |
MOXIDECTIN plasma | Homo sapiens |
|
176 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03012828 |
24 mg single, oral dose: 24 mg route of administration: oral experiment type: single co-administered: |
MOXIDECTIN plasma | Homo sapiens |
|
247 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03012828 |
36 mg single, oral dose: 36 mg route of administration: oral experiment type: single co-administered: |
MOXIDECTIN plasma | Homo sapiens |
|
27.2 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03012828 |
4 mg single, oral dose: 4 mg route of administration: oral experiment type: single co-administered: |
MOXIDECTIN plasma | Homo sapiens |
|
56.7 ng/mL Clinical Trial https://clinicaltrials.gov/ct2/show/NCT03012828 |
8 mg single, oral dose: 8 mg route of administration: oral experiment type: single co-administered: |
MOXIDECTIN plasma | Homo sapiens |
AUC
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Dose | Population | Adverse 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%) Sources: Page: 3Pruritus (65%) Musculoskeletal pain (64%) Headache (58%) Lymphocytopenia (48%) Tachycardia (39%) Postural orthostatic tachycardia syndrome (34%) Tachycardia (18%) Rash (37%) Abdominal pain (31%) |
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%) Sources: Page: 4Orthostatic 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%) |
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%) Sources: Page: 5Lymphocytopenia (grade 3, 23%) Neutrophils (grade 4, 7%) |
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... |
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... |
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%) Sources: Page: 13Rash (41%) Postural orthostatic tachycardia syndrome (48%) Orthostatic hypotension (18%) Lymph node pain (20%) |
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%) Sources: Page: 13Rash (53%) Postural orthostatic tachycardia syndrome (31%) Orthostatic hypotension (29%) Lymph node pain (36%) |
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%) Sources: Page: 13Rash (63%) Postural orthostatic tachycardia syndrome (63%) Orthostatic hypotension (60%) Lymph node pain (63%) |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| 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 |
Overview
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no | ||||
| no | ||||
| no | ||||
| no | ||||
| no | no (co-administration study) Comment: no in vivo drug-drug interaction between moxidectin and the CYP3A4 substrate, midazolam Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210867Orig1s000ClinPharmR.pdf#page=43 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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2018/210867Orig1s000ClinPharmR.pdf#page=43 Page: 8;12;43;53 |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| limited | ||||
| limited | ||||
| limited | ||||
| major | ||||
| major | ||||
| no | ||||
| no | ||||
| weak | ||||
| yes | ||||
| yes | ||||
| yes |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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
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SUBSTANCE RECORD
