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ドラメクチン

Doramectin

HCID 9832750
ノートを作成反応を作成見積依頼を出す印刷プレビュー
基本情報概要名称と識別子物性安全と法規制化学と産業関連反応化合物ノート
部分構造検索類似構造を探す

基本情報

CAS
117704-25-3
標準SMILES
CO[C@H]1C[C@H](O[C@H]2[C@H](C)O[C@@H](O[C@@H]3/C(C)=C/C[C@@H]4C[C@@H](C[C@]5(C=C[C@H](C)[C@@H](C6CCCCC6)O5)O4)OC(=O)[C@@H]4C=C(C)[C@@H](O)[C@H]5OC/C(=C\C=C\[C@@H]3C)[C@]54O)C[C@@H]2OC)O[C@@H](C)[C@@H]1O
InChIKey
QLFZZSKTJWDQOS-YDBLARSUSA-N
分子式
C50H74O14
平均分子量
899.1 g/mol
単同位体質量
898.50785703

概要

Doramectin is a veterinary drug approved by the Food and Drug Administration for the treatment of parasites such as gastrointestinal roundworms, lungworms, eyeworms, grubs, sucking lice and mange mites in cattle.

名称と識別子

優先名称
Doramectin
IUPAC
(1'R,2R,3S,4'S,6S,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-2-cyclohexyl-21',24'-dihydroxy-12'-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one
現地名
ドラメクチン
英語名
Doramectin
分子式
C50H74O14
分子量
899.11

名称と別名

Doramectin117704-25-3DoramectinaDoramectineDoramectinumDectomaxDTXSID9048982UK 67994UK-67994UK-67,994KGD7A54H5PNSC-760342
名称をさらに表示
5-O-デメチル-25-デ(1-メチルプロピル)-25-シクロヘキシルアベルメクチンA1aドラメクチン5-デメトキシ-5-ヒドロキシ-25-デ(1-メチルプロピル)-25-シクロヘキシルアベルメクチンA1a25-シクロヘキシル-5-O-デメチル-25-デ(1-メチルプロピル)アベルメクチンA1aドラメクチン標準品ドラメクチン 合成品ドラメクチン (JAN)5-O-デメチル-25-デ(1-メチルプロピル)-25-シクロヘキシルエバーメクチンA1a(1'R,2S,4'S,5S,6R,8'R,12'S,13'S,16'Z,20'R,21'R,24'S)-6-シクロヘキシル-21',24'-ジヒドロキシ-12'-{[(2R,4S,5S,6S)-5-{[(2S,4S,5S,6S)-5-ヒドロキシ-4-メトキシ-6-メチルオキサン-2-イル]オキシ}-4-メトキシ-6-メチルオキサン-2-イル]オキシ}-5,11',13',22'-テトラメチル-5,6-ジヒドロ-3',7',19'-トリオキサスピロ[ピラン-2,6'-テトラシクロ[15.6.1.14,8.020,24]ペンタコサン]-10',14',16',22'-テトラエン-2'-オン5-デメトキシ-5-ヒドロキシ-25-デ(1-メチルプロピル)-25-シクロヘキシルエバーメクチンA1a25-シクロヘキシル-5-O-デメチル-25-デ(1-メチルプロピル)エバーメクチンA1a

物性

構造計算による物性

XLogP
4.5
極性表面積
170 Ų
水素結合供与体数
3
水素結合受容体数
14
回転可能結合数
7
重原子数
64
形式電荷
0
複雑度
1,790

実験および物理化学的性質

PesticidesPesticide (Doramectin) -> USDA PDB
Animal DrugsFDA approved animal drugs -> Active ingredient
Melting Point116-119 °C
Collision Cross Section308.14 Ų [M+Na]+

物理化学的性質

融点
116 · 116-1190C
沸点
967.4 · 967.4±65.0 °C(Predicted)
比重(密度)
1.25 · 1.25±0.1 g/cm3(Predicted)
蒸気圧
0 Pa · 0Pa at 20℃
貯蔵温度
-20 °C · Sealed in dry,Store in freezer, under -20°C
溶解性
メタノール: 可溶
外見
個体
酸解離定数(Pka)
12.42 · 12.42±0.70(Predicted)
色
白い
InChIKey
QLFZZSKTJWDQOS-YDBLARSUSA-N
LogP
4.39 · 4.39-4.43 at 25℃

化学的性質

安全と法規制

安全情報は参考情報です。供給元の安全データシート(SDS)、適用法令、専門家による評価に代わるものではありません。

GHS分類

GHS Classification · 4 件

Danger

H300 (33.3%): Fatal if swallowed [Danger Acute toxicity, oral]

P203, P260, P263, P264, P270, P273, P280, P301+P316, P301+P317, P308+P316, P318, P319, P321, P330, P391, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 111 reports by companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

危険有害性情報

Regulatory Information · 2 件

REACH registered substance: Avermectin A(sub 1a), 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)- (EC: 601-490-4)

Doramectin: Does not have an individual approval but may be used under an appropriate group standard

FDA Requirements · 3 件

Implantation or injectable dosage form new animal drugs. Doramectin: Conditions of use (1) cattle ... Indications for use. For treatment and control of gastrointestinal roundworms, lungworms, eyeworms, grubs, sucking lice, and mange mites. To control infections and to protect from reinfection with Cooperia oncophora and Haemonchus placei for 14 days, Ostertagia ostertagi for 21 days, and C. punctata, Oesophagostomum radiatum, and Dictyocaulus viviparus for 28 days after treatment. ... (2) Swine ... Indications for use. For treatment and control of gastrointestinal roundworms, lungworms, kidney worms, sucking lice, and mange mites.

Ophthalmic and topical dosage form new animal drug. Doramectin: Conditions of use in cattle ... Indications for use. For treatment and control of gastrointestinal roundworms: Ostertagia ostertagi (adults and fourth-stage larvae), Ostertagia ostertagi (inhibited fourth-stage larvae), Ostertagia lyrata (adults), Haemonchus placei (adults and fourth-stage larvae), Trichostrongylus axei (adults and fourth-stage larvae), Trichostrongylus colubriformis (adults and fourth-stage larvae), Cooperia oncophora (adults and fourth-stage larvae), Cooperia punctata (adults and fourth-stage larvae), Cooperia pectinata (adults), Cooperia surnabada (adults), Bunostomum phlebotomum (adults), Oesophagostomum radiatum (adults and fourth-stage larvae), Trichuris spp. (adults); lungworms: Dictyocaulus viviparus (adults and fourth-stage larvae); eyeworms: Thelazia gulosa (adults), Thelazia skrjabini (adults); grubs: Hypoderma bovis and Hypoderma lineatum; sucking lice: Linognathus vituli, Haematopinus eurysternus, and Solenopotes capillatus; biting lice: Bovicola (Damalinia) bovis; mange mites: Chorioptes bovis and Sarcoptes scabiei; horn flies: Haematobia irritans; and to control infections and to protect from reinfection with Cooperia oncophora, Dictyocaulus viviparus, Ostertagia ostertagi, and Oesophagostomum radiatum for 28 days; and with Cooperia punctata and Haemonchus placei for 35 days after treatment; and to control infestations and to protect from reinfestation with Linognathus vituli for 42 days and with Bovicola (Damalinia) bovis for 77 days after treatment.

化学と産業

薬理情報

ATC CodeQP - Antiparasitic products, insecticides and repellents
Mechanism of Action · 1 件

Avermectins induce rapid, non-spastic paralysis in nematodes and arthropods. One common feature of avermectins appears to be the modulation of trans-membrane chloride ion (Cl-) channel activity in nematode nerve cells, and in both nerve and muscle cells of arthropods. These Cl- channels may be gated by a variety of neurotransmitter receptors including gamma-aminobutyric acid (GABA), glutamate and acetylcholine. Activation of the Cl- channels by avermectins leads to an increase in Cl- conductance which results in a changed membrane potential and this causes inhibition of electrical activity in the target nerve or muscle cell. GABA is also a major inhibitory neurotransmitter in the mammalian CNS and avermectins do have intrinsic activity on the mammalian GABA receptor/Cl- channel complex. Avermectins have been reported to bind to glycine receptor/Cl- channel complexes which are restricted to the CNS in mammals. Penetration of the blood brain barrier by avermectins is extremely poor and this may account for the wide margin of safety exhibited by these compounds following administration to mammals. /Avermectins/

Biological Half-Life · 1 件

The plasma kinetics of doramectin were determined in eight pigs (4 male castrates and 4 females, each weighing approximately 40 kg) dosed im with (3H)doramectin at 0.3 mg/kg bw using a prototype commercial formulation (75% sesame oil/25% ethyl oleate). ... The apparent terminal half-lives of elimination from plasma of total (3H)labelled materials and unchanged doramectin were 7.7 and 6.4 days, respectively.

Metabolism/Metabolites · 2 件

Doramectin labelled with tritium in the 5-position was administered as a single dose to Sprague-Dawley rats (2 males given 5 mg/kg bw in propylene glycol:glycerol by gavage), a beagle dog (1 female given 3.5 mg/kg bw in sesame oil by gavage) and cattle (5 males given 0.2 mg/kg bw subcutaneously). /The following metabolites were identified in/... the liver and feces from each species and the fat of cattle... /unchanged doramectin, 3"-O-desmethyl doramectin, 24-hydroxymethyl doramectin, and 24-hydroxymethyl-3"-O-desmethyl doramectin./

The products of doramectin metabolism were similar in all species investigated /rats, dogs, pigs, cattle/. The metabolites were more polar than doramectin and were the result of O-demethylation in the distal saccharide ring, of hydroxylation of the 24-methyl group and a combination of both of these biotransformations.

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化合物ノート

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このページの内容基本情報概要名称と識別子物性安全と法規制化学と産業関連反応化合物ノート
CS-837
Dectoma
DM/CBR15
Hsdb 7452
Doramecin
VMF ready
Avermectin A1a, 25-cyclohexyl-5-O-demethyl-25-de(1-methylpropyl)-L-701023DTXCID5028908L 701023DorajectDectoGardDectomax Pour-On(1'R,2R,3S,4'S,6S,8'R,10'E,12'S,13'S,14'E,16'E,20'R,21'R,24'S)-2-cyclohexyl-21',24'-dihydroxy-12'-[(2R,4S,5S,6S)-5-[(2S,4S,5S,6S)-5-hydroxy-4-methoxy-6-methyloxan-2-yl]oxy-4-methoxy-6-methyloxan-2-yl]oxy-3,11',13',22'-tetramethylspiro[2,3-dihydropyran-6,6'-3,7,19-trioxatetracyclo[15.6.1.14,8.020,24]pentacosa-10,14,16,22-tetraene]-2'-one

データベース識別子

CAS
117704-25-3
PubChem CID
9832750
DTXSID
DTXSID9048982
ChEMBL
CHEMBL2361641
UNII
KGD7A54H5P
EC Number
601-490-4、923-471-2
Nikkaji
J3.421.994J

化学的特性White solid or slightly yellow-brown powder with poor water solubility, low stability, easily decomposed and deactivated by sunlight. The remaining drug residue is toxic to fish and aquatic organisms, requiring water source protection.

Tolerances for residues of new animal drugs in food. Doramectin. a) Acceptable daily intake (ADI). The ADI for total residues of doramectin is 0.75 microgram per kilogram of body weight per day. (b) Tolerances - (1) Cattle. A tolerance of 100 parts per billion is established for parent doramectin (marker residue) in liver (target tissue) and of 30 parts per billion for parent doramectin in muscle. (2) Swine. A tolerance is established for parent doramectin (marker residue) in liver (target tissue) of 160 parts per billion.

Hazard Classes and CategoriesAcute Tox. 1 (33.3%)

安全と保護具

Preventive Measures · 2 件

If material not on fire and not involved in fire: Keep sparks, flames, and othersources of ignition away. Keep material out of water sources and sewers. /Organochlorine pesticide, solid, NOS/

Personnel protection: Avoid breathing dusts, and fumes from burning material. Keep upwind. Avoid bodily contact with the material. ... Do not handle broken packages unless wearing appropriate personal protective equipment. Wash away any material which may have contacted the body with copious amounts of water or soap and water. ... If contact with the material anticipated, wear appropriate chemical protective clothing. /Organochlorine pesticide, solid, NOS/

Personal Protective Equipment (PPE)Wear appropriate chemical protective gloves, boots, and goggles. /Organochlorine pesticide, solid or liquid, NOS/

毒性情報

Ecotoxicity Values · 3 件

LC50 Eisenia foetida (earthworm) >1000 ppm/28 days, artificial soil

LC50 Onchorhynchus mykiss (rainbow trout) 5.1 ppb/96 hr, static

LC50 Lepomis macrochirus (bluegill sunfish) 11 ppb/96 hr, static

Ecotoxicity Excerpts · 5 件

/OTHER TERRESTRIAL SPECIES/ The acute oral (single dose) LD50 of doramectin for Bobwhite quail lies in excess of 2000 mg/kg. Following doses of 500, 1000 or 2000 mg/kg, clinical signs of toxicity were mild and only infrequently observed; those receiving 2000 mg/kg were necropsied 14 days post dose and no abnormalities were observed.

/OTHER TERRESTRIAL SPECIES/ No mortality was observed in the /redworm/ Eisenia fetida exposed to 1000 ppm doramectin in an artificial soil for 28 days. The 28 day LC50 is therefore >1000 ppm. Based on weight gain, the most sensitive criteria monitored, the NOEC was 2 ppm and the LOEC was 4 ppm.

/OTHER TERRESTRIAL SPECIES/ Adult worms /Eisenia fetida (redworm)/ were exposed to doramectin for 56 days and showed no effects except for worms exposed to the highest concentration (17 mg/kg) requiring longer time to burrow. Juvenile production was reduced in worms exposed to a doramectin concentration of 1.6 mg/kg or higher. The no observed effect concentration based on fecundity data was 0.89 mg/kg doramectin.

/OTHER TERRESTRIAL SPECIES/ Adult worms /Enchytraeus albidus (whiteworm)/ were exposed to doramectin for 42 days and no effects were observed at any concentration. Juvenile production was reduced in worms exposed to a doramectin concentration of 24 mg/kg or higher. The no observed effect concentration based on fecundity data was 13 mg/kg doramectin.

For more Ecotoxicity Excerpts (Complete) data for DORAMECTIN (7 total), please visit the HSDB record page.

Non-Human Toxicity Excerpts · 5 件

/LABORATORY ANIMALS: Acute Exposure/ Doramectin was applied to normal and abraded skin of 3 New Zealand white rabbits (0.5 g under an occlusive patch) for 24 hours. Slight erythema was observed 24 and 48 hours post-dose at 1 of 3 intact sites and 2 of 3 abraded sites. There was no edema at any site and all sites appeared normal 72 hours post-dose.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Groups of CD-1 mice (10/sex/dose) were administered doramectin (purity 94.1%) in the diet for 43 days. Target doses were 0, 10, 20, 40, or 60 mg/kg bw/day on days 1 to 14; 0, 10, 20, 80 or 100 mg/kg bw/day on days 15 to 28; and 0, 100, 200, 400 or 600 mg/kg bw/day on days 29 to 43. Toxic signs included lethargy, hunched posture and tremors at 400 and 600 mg/kg bw/day, and hunched and ungroomed appearance in some mice at 100 and 200 mg/kg bw/day. A number of animals given 400 and 600 mg/kg bw/day were sacrificed moribund and the remaining mice in these groups were killed on day 33. There were no effects on body weight or food consumption. Relative liver weights were slightly higher in most treated groups but the changes were minor and not dose-related. Clinical laboratory parameters and pathological examinations were not carried out.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Groups of CD-1 mice (10/sex/group) were fed doramectin (purity 94.1%) in the diet for 92 days. Target doses were 0, 100, 200 or 300 mg/kg bw/day. Actual doramectin intake was 83-121, 154-191 or 221-322 mg/kg bw/day. Tremors, hunched posture, unkempt appearance and lethargy were observed at the mid- and high-dose groups and resulted in death or moribund sacrifice of 9 mice at 300 mg/kg bw/day and 3 mice at 200 mg/kg bw/day. The remaining animals in these two groups were killed on day 12 or 19, respectively. Body-weight gain was depressed in association with reduced food consumption at 200 mg/kg bw/day and above. Serum creatinine and BUN were slightly increased at 100 mg/kg bw/day with no effects at higher doses, presumably due to early culling of mice in these groups. Hematological parameters were unaffected. All treated groups had increased liver weights and hypertrophy of centrilobular hepatocytes, with multinucleate non-proliferative liver cells at 100 mg/kg bw/day only. Dead and moribund animals showed lymphocyte lysis in lymphoid organs, cellular depletion of bone marrow and necrosis of the adrenal cortex which may have resulted from stress and weight loss.

/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ Groups of Long-Evans rats (10/sex/group) were fed a diet containing doramectin (purity 94.1%) at levels intended to give target doses of 0, 20, 40, 60 or 80 mg/kg bw/day for 38 days. Chromorhinorrhea, chromodacryorrhea and urogenital staining were seen at 40 mg/kg bw/day and above. Whole body tremors were also present at the two highest doses and resulted in the sacrifice of 2 rats at 60 mg/kg bw/day and all rats at 80 mg/kg bw/day. Body-weight gain and food consumption were lower at 60 mg/kg bw/day and above. Serum 5'-nucleotidase was increased at 80 mg/kg bw/day with elevated levels of blood urea nitrogen at 40 mg/kg bw/day and above. Liver weights were higher in the 40 and 60 mg/kg bw/day groups but with no dose relationship.

For more Non-Human Toxicity Excerpts (Complete) data for DORAMECTIN (9 total), please visit the HSDB record page.

Antidote and Emergency Treatment · 2 件

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

Acceptable Daily IntakesThe ADI for total residues of doramectin is 0.75 microgram per kilogram of body weight per day.
Non-Human Toxicity Values · 2 件

LD50 Mouse (CD-1) oral >2000 mg/kg bw /in 0.1% aqueous methylcellulose/ /from table/

LD50 Rat (Sprague-Dawley, male) ip >300 mg/kg bw /in 0.1% aqueous methylcellulose/ /from table/

法規制情報

FDA Requirements · 3 件

Implantation or injectable dosage form new animal drugs. Doramectin: Conditions of use (1) cattle ... Indications for use. For treatment and control of gastrointestinal roundworms, lungworms, eyeworms, grubs, sucking lice, and mange mites. To control infections and to protect from reinfection with Cooperia oncophora and Haemonchus placei for 14 days, Ostertagia ostertagi for 21 days, and C. punctata, Oesophagostomum radiatum, and Dictyocaulus viviparus for 28 days after treatment. ... (2) Swine ... Indications for use. For treatment and control of gastrointestinal roundworms, lungworms, kidney worms, sucking lice, and mange mites.

Ophthalmic and topical dosage form new animal drug. Doramectin: Conditions of use in cattle ... Indications for use. For treatment and control of gastrointestinal roundworms: Ostertagia ostertagi (adults and fourth-stage larvae), Ostertagia ostertagi (inhibited fourth-stage larvae), Ostertagia lyrata (adults), Haemonchus placei (adults and fourth-stage larvae), Trichostrongylus axei (adults and fourth-stage larvae), Trichostrongylus colubriformis (adults and fourth-stage larvae), Cooperia oncophora (adults and fourth-stage larvae), Cooperia punctata (adults and fourth-stage larvae), Cooperia pectinata (adults), Cooperia surnabada (adults), Bunostomum phlebotomum (adults), Oesophagostomum radiatum (adults and fourth-stage larvae), Trichuris spp. (adults); lungworms: Dictyocaulus viviparus (adults and fourth-stage larvae); eyeworms: Thelazia gulosa (adults), Thelazia skrjabini (adults); grubs: Hypoderma bovis and Hypoderma lineatum; sucking lice: Linognathus vituli, Haematopinus eurysternus, and Solenopotes capillatus; biting lice: Bovicola (Damalinia) bovis; mange mites: Chorioptes bovis and Sarcoptes scabiei; horn flies: Haematobia irritans; and to control infections and to protect from reinfection with Cooperia oncophora, Dictyocaulus viviparus, Ostertagia ostertagi, and Oesophagostomum radiatum for 28 days; and with Cooperia punctata and Haemonchus placei for 35 days after treatment; and to control infestations and to protect from reinfestation with Linognathus vituli for 42 days and with Bovicola (Damalinia) bovis for 77 days after treatment.

Tolerances for residues of new animal drugs in food. Doramectin. a) Acceptable daily intake (ADI). The ADI for total residues of doramectin is 0.75 microgram per kilogram of body weight per day. (b) Tolerances - (1) Cattle. A tolerance of 100 parts per billion is established for parent doramectin (marker residue) in liver (target tissue) and of 30 parts per billion for parent doramectin in muscle. (2) Swine. A tolerance is established for parent doramectin (marker residue) in liver (target tissue) of 160 parts per billion.

安全データ

wgk
3
ridadr
UN 2811 6.1/PG 3
hs_code
29419090
risk_code
25-50/53-36/37/38
hazard_code
T,N,Xi
safety_code
33-45-60-61-36/37-26
有毒物質データの
117704-25-3(Hazardous Substances Data)
MeSH Pharmacological Classification · 4 件

Agents that kill parasitic worms. They are used therapeutically in the treatment of HELMINTHIASIS in man and animal.

Drugs used to prevent SEIZURES or reduce their severity.

Pesticides designed to control insects that are harmful to man. The insects may be directly harmful, as those acting as disease vectors, or indirectly harmful, as destroyers of crops, food products, or textile fabrics.

Agents that alleviate ANXIETY, tension, and ANXIETY DISORDERS, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. ADRENERGIC BETA-ANTAGONISTS are commonly used in the symptomatic treatment of anxiety but are not included here.

Absorption, Distribution and Excretion · 5 件

In the first study, 10 dairy Holstein cows were treated with a pour-on formulation of doramectin at a dose of 0.58 mg/kg bw and were retreated with the same dose 56 days later. ... Samples of milk were collected for 49 days and 10 days, respectively, after the first and second treatments. Samples were collected twice daily until day 7, and once daily on days 10, 13, 16, 19, 22, 25, 28, 32, 36, 40 and 49. On retreatment, samples were taken twice daily until day 7 and once at day 10. ... The concentrations of doramectin residue in milk increased to a maximum mean value of 22 mg/kg at 72 hr after treatment. Mean concentrations of doramectin residues decreased to below the limit of quantitation (3 mg/kg) at 384 hr (16 days). After retreatment, concentrations of doramectin residues increased gradually to a maximum mean value of 12 mg/kg at 48 hr after dosing; and decreased to <4 mg/kg at 240 hr (10 days) after dosing. The milk/fat analyses were conducted 1, 4, and 10 days after dosing. Mean concentrations of doramectin residues in the milk fat at these time points were 171 mg/kg, 501 mg/kg and 114 mg/kg, respectively. Concentration factors for doramectin residues in milk fat were 29.6, 32.2 and 24.7, respectively.

In the second study, 10 cows were treated with doramectin by topical application of a pour-on formulation at a dose of 0.58 mg/kg and were re-treated with the same dose 56 days later. Samples of milk were collected twice daily. Concentrations of doramectin in milk increased to a maximum mean value of 9 mg/kg at 45 hr after treatment and decreased to below the LOQ by 237 hr (10 days) after treatment. After re-treatment on day 56, concentrations of residues increased to a mean maximum value of 8 mg/kg after 93 hr and decreased to less than the LOQ after 237 hr (10 days). Mean concentrations of doramectin residues in the milk fat at 1, 4, and 10 days were 91 mg/kg, 142 mg/kg and 55 mg/kg, respectively. Concentration factors for doramectin residues in milk fat versus milk were 14.2, 20.9 and 14.1, respectively.

The third study determined the residue depletion profile of doramectin following the subcutaneous administration of doramectin formulation at 0.23 mg/kg bw in lactating cattle, followed by retreatment at the same dose 56 days later. ... Doramectin concentrations in milk increased gradually to a maximum mean value of 45 mg/kg at 67 hr. Subsequently, doramectin residues gradually declined, with mean residues below LOQ at 523 hr (22 days). After re-treatment, doramectin residues increased to a maximum mean value of 53 mg/kg at 56 hr. Residue concentrations then decreased to a mean value of 25 mg/kg at 237 hr (10 days) after re-treatment. Residues resulting from treatment by injection were consistently higher at any given timepoint than were those resulting from treatment with the pour-on formulation. Milk fat analyses were conducted using samples collected at the morning milking on days 1, day 4 and day 10 after treatment. Mean concentrations of doramectin residues in milk fat at these time-points were 557 mg/kg, 1036 mg/kg and 354 mg/kg, respectively. Milk fat concentration factors were 24, 24.2 and 23.4, respectively.

Self-licking behavior in cattle has recently been identified as a determinant of the kinetic disposition of topically-administered ivermectin. /The present study documents/ the occurrence and extent of transfer between cattle of three topically-administered endectocides, as a consequence of allo-licking. Four groups of two Holstein cows each received one pour-on formulation of doramectin, ivermectin, or moxidectin, or no treatment. The cows were then kept together in a paddock. Systemic exposure to each topically-administered endectocide was observed in at least five of six non-treated cattle. Plasma and fecal drug concentration profiles in non-treated animals were highly variable between animals and within an animal, and sometimes attained those observed in treated animals. Drug exchanges were quantified by measuring plasma and fecal clearances after simultaneous i.v. administration of the three drugs as a cocktail. Plasma clearances were 185 + or - 43, 347 + or - 77 and 636 + or - 130 ml/kg/day, fecal clearances representing 75 + or - 26, 28 + or - 13, and 39 + or - 30% of the plasma clearance for doramectin, ivermectin and moxidectin, respectively. The amount of drug ingested by non-treated cattle attained 1.3-21.3% (doramectin), 1.3-16.1% (ivermectin), 2.4-10.6% (moxidectin) of a pour-on dose (500 ug/kg). The total amount of drug ingested by all non-treated cattle represented 29% (doramectin), 19% (ivermectin), and 8.6% (moxidectin) of the total amount of each drug poured on the backs of treated animals. The cumulative amounts of endectocide ingested by each non-treated cow ranged from 1.3 to 27.4% of a pour-on dose. Oral bioavailability after drug ingestion due to allo-licking was 13.5 + or - 9.4, 17.5 + or - 3.5 and 26.1+ or - 11.1% for doramectin, ivermectin and moxidectin, respectively. The extent of drug exchange demonstrated here raises concerns for drug efficacy and safety, emergence of drug resistance, presence of unexpectedly high residue levels in treated and/or untreated animals and high environmental burdens.

For more Absorption, Distribution and Excretion (Complete) data for DORAMECTIN (7 total), please visit the HSDB record page.

用途と製造

Uses · 3 件

Therap cat (vet): antiparasitic

... Control of certain gastrointestinal roundworms, lungworms, eyeworms, kidney worms, grubs, lice, and mange mites (in cattle and swine)[US FDA; Animal Drugs, Feeds, and Related Products: Doramectin. Federal Register: November 21, 1997 (Volume 62, Number 225)] [Rules and Regulations]

MEDICATION (VET)

Methods of Manufacturing · 2 件

... S.P. Gibson et al., European patent 214,731; /corresponds to/ US patent 5,089,480 (1987, 1992 both to Pfizer).

... Fermentation product of a specific strain of Streptomyces avermitilis ... .

Use ClassificationVeterinary Drug -> ANTHELMINTHIC_AGENT -> JECFA Functional Classes
General Manufacturing Information · 2 件

Doramectin is not approved for use in female dairy cattle 20 months of age or older. If a lactating cow is exposed to Doramectin, milk from the cow may have detectable residues of the drug for as long as 60 days. Any detectable level of Doramectin in milk is considered by FDA to be illegal.

The avermectin eprinomectin, which is analogous to doramectin, can reduce dung beetle populations in pastures where the cattle have been treated with pour-on formulations.

応用分野 · 2 件

説明Doramectin[117704-25-3] is a novel avermectin with a cyclohexyl substituent on the previously inaccessible C-25 position of the molecule; the substitution was facilitated by mutational biosynthesis. The discovery of doramectin involved feeding carboxylic acids or their precursors to a fermentation of Streptomyces avermitilis that lacked branched-chain 2-oxo acid dehydrogenase activity, and then screening the resultant fermentation products for anthelmintic and ectoparasiticidal activity. Two dosage forms of doramectin have been developed for use as an endectocide on cattle, an injectable formulation for subcutaneous administration and a pouron formulation. An injectable formulation is also approved for use on pigs.

使用Doramectin is a biosynthetic avermectin derived from a mutant strain of Streptomyces avermitilis, supplemented with a cyclohexylcaboxylic acid starting unit. Doramectin was developed as an anthelmintic for internal parasite control. The presence of the cyclohexyl group replacing the sec-butyl moiety affords greater hydrophobicity and longer biological half-life compared to avermectin. Like the other milbemycin/avermectins, it selectively binds to parasite glutamate-gated chloride ion channels and disrupts neurotransmission leading to paralysis and death of the parasite.