Artemether

Các tên gọi khác (11 ) :

(1R,4S,5R,8S,9R,10S,12R,13R)-10-Methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecane
10-Methoxy-1,5,9-trimethyl-(1R,4S,5R,8S,9R,10S,12R,13R)-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecane
Artemetero
Artemetherum
Artemisininelactol methyl ether
beta-Artemether
beta-Dihydroartemisinin methyl ether
Dihydroartemisinin methyl ether
Dihydroqinghaosu methyl ether
Methyl-dihydroartemisinine
SM-224

Thuốc trị ký sinh trùng, chống nhiễm khuẩn

Thuốc Gốc

Small Molecule

CAS: 71963-77-4

ATC: P01BE02

CTHH: C₁₆H₂₆O₅

PTK: 298.3746

Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas.

Nhận Dạng Quốc Tế & Đặc Tính Hóa Học

Công thức hóa học

C₁₆H₂₆O₅

Phân tử khối

298.3746

Monoisotopic mass

298.178023942

InChI

InChI=1S/C16H26O5/c1-9-5-6-12-10(2)13(17-4)18-14-16(12)11(9)7-8-15(3,19-14)20-21-16/h9-14H,5-8H2,1-4H3/t9-,10-,11+,12+,13+,14-,15-,16-/m1/s1

InChI Key

InChIKey=SXYIRMFQILZOAM-HVNFFKDJSA-N

IUPAC Name

(1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecane

Traditional IUPAC Name

(1R,4S,5R,8S,9R,10S,12R,13R)-10-methoxy-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0^{4,13}.0^{8,13}]hexadecane

SMILES

[H][C@@]12CC[C@@H](C)[C@]3([H])CC[C@@]4(C)OO[C@@]13[C@]([H])(O[C@H](OC)[C@@H]2C)O4

Độ tan chảy

86-90

Độ hòa tan

Insoluble

logP

3.53

logS

-2.8

pKa (Strongest Basic)

-3.9

PSA

46.15 Å²

Refractivity

74.66 m³·mol^-1

Polarizability

32.12 Å³

Rotatable Bond Count

H Bond Acceptor Count

H Bond Donor Count

Physiological Charge

Number of Rings

Bioavailability

Rule of Five

true

Ghose Filter

true

Dược Lực Học : In the body, artemether is metabolized into the active metabolite metabolite dihydroartemisinin. The drug works against the erythrocytic stages of P. falciparum by inhibiting nucleic acid and protein synthesis. Artemether is administered in combination with lumefantrine for improved efficacy. Artemether has a rapid onset of action and is rapidly cleared from the body. It is thought that artemether provides rapid symptomatic relief by reducing the number of malarial parasites. Lumefantrine has a much longer half life and is believed to clear residual parasites.

Cơ Chế Tác Dụng : Artemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy. This combination therapy exerts its effects against the erythrocytic stages of Plasmodium spp. and may be used to treat infections caused by P. falciparum and unidentified Plasmodium species, including infections acquired in chloroquine-resistant areas. Involves an interaction with ferriprotoporphyrin IX (“heme”), or ferrous ions, in the acidic parasite food vacuole, which results in the generation of cytotoxic radical species. The generally accepted mechanism of action of peroxide antimalarials involves interaction of the peroxide-containing drug with heme, a hemoglobin degradation byproduct, derived from proteolysis of hemoglobin. This interaction is believed to result in the formation of a range of potentially toxic oxygen and carbon-centered radicals.

Dược Động Học :

▧ Absorption :
Food increases absorption.
▧ Protein binding :
Artemether and lumefantrine are both highly bound to human serum proteins in vitro (95.4% and 99.7%, respectively). Dihydroartemisinin is also bound to human serum proteins (47% to 76%).
▧ Metabolism :
Rapidly metablized to its active metabolite, dihydroartemisinin.
▧ Half Life :
Artemether, 1.6 +/- 0.7 and 2.2 +/- 1.9 hr; Dihydroartemisinin, 1.6 +/- 0.6 and 2.2 +/- 1.5 hr

Độc Tính : Animal studies on acute toxicity show that the LD50 of Artemether in mice is a single i.g. administration of 895mg/kg and a single i.m. injection of 296mg/kg dose; in rats, the LD50 is a single i.m. injection of 597mg/kg dose.

Chỉ Định : Artemether and lumefantrine combination therapy is indicated for the treatment of acute uncomplicated malaria caused by Plasmodium falciparum, including malaria acquired in chloroquine-resistant areas. May also be used to treat uncomplicated malaria when the Plasmodium species has not been identified. Indicated for use in adults and children greater than 5 kg.

Tương Tác Thuốc :

Amiodarone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Amitriptyline Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Amoxapine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Apomorphine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Arsenic trioxide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Asenapine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Azithromycin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Bepridil Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Chloroquine Chloroquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Chlorpromazine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Cisapride Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Citalopram Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Clarithromycin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Clomipramine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Conivaptan Conivaptan, a strong CYP3A inhibitor, may increase the toxicity of artemether by inhibiting its metabolism. Consider alternate therapy or allow at least 7 days to elapse between conivaptan and artemether therapy.
Dasatinib Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Degarelix Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Desipramine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Desogestrel Artemether may decrease the effectiveness of desogestrel by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Disopyramide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Dofetilide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Dolasetron Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Domperidone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Doxepin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Dronedarone Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.
Droperidol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Drospirenone Artemether may decrease the effectiveness of drospirinone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Erythromycin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Escitalopram Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ethinyl Estradiol Artemether may decrease the effectiveness of ethinyl estradiol by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Ethynodiol Artemether may decrease the effectiveness of ethynodiol diacetate by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Etonogestrel Artemether may decrease the effectiveness of etonogestrel by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Etravirine Artemether, when administered concomitantly with etravirine, may experience a decrease in serum concentrations of active metabolites such as dihydroartemisinin; however, artemether may increase in serum concentration. Etravirine, when used with artemether, may increase in serum concentration. Caution and monitoring of therapeuric efficacy of artemether is recommended.
Flecainide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Fluconazole Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Fluoxetine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Flupentixol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Foscarnet Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Gadobutrol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Gadofosveset trisodium Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Halofantrine Halofantrine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Haloperidol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Hydroxychloroquine Hydroxychloroquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Ibutilide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Iloperidone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Imipramine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Indapamide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Isradipine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ketoconazole Concurrent oral administration of ketoconazole, a potent CYP3A4 inhibitor, with a single dose of Coartem Tablets resulted in a moderate increase in exposure to artemether, DHA, and lumefantrine in a study of 15 healthy subjects.
Lapatinib Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Levofloxacin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Levonorgestrel Artemether may decrease the effectiveness of levonorgestrel by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Loxapine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Maprotiline Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Medroxyprogesterone Acetate Artemether may decrease the effectiveness of medroxyprogesterone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Mefloquine Mefloquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Mesoridazine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Mestranol Artemether may decrease the effectiveness of mestranol by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Methadone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Methotrimeprazine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Moxifloxacin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Nilotinib Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Norelgestromin Artemether may decrease the effectiveness of norelgestromin by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Norethindrone Artemether may decrease the effectiveness of norethindrone by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Norfloxacin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Norgestimate Artemether may decrease the effectiveness of norgestimate by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Nortriptyline Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Octreotide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pazopanib Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pentamidine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Perflutren Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pimozide Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.
Primaquine Primaquine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Probucol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Procainamide Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Proguanil Proguanil may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Propafenone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Protriptyline Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Pyrimethamine Pyrimethamine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Quetiapine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Quinidine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Quinine Quinine may increase the adverse effects of artemether. Combination therapy is contraindicated unless there are no other treatment options.
Ranolazine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Rifampicin Oral administration of rifampin, a strong CYP3A4 inducer, with Coartem Tablets resulted in significant decreases in exposure to artemether, dihydroartemisinin (DHA, metabolite of artemether) and lumefantrine by 89%, 85% and 68%, respectively, when compared to exposure values after Coartem Tablets alone. Concomitant use of strong inducers of CYP3A4 such as rifampin, carbamazepine, phenytoin and St. John’s wort is contraindicated with Coartem Tablets.
Risperidone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Romidepsin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Saquinavir Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Sotalol Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Sparfloxacin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Sunitinib Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tacrolimus Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Telavancin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Telithromycin Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Tetrabenazine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Thioridazine Additive QTc-prolongation may occur. Concomitant therapy is contraindicated.
Thiothixene Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Toremifene Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Trimipramine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Voriconazole Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Vorinostat Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
Ziprasidone Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Liều Lượng & Cách Dùng : Tablet - Oral - Artemether 20 mg, Lumefantrine 120 mg

Tài Liệu Tham Khảo Thêm

drugbank

http://www.drugbank.ca/drugs/DB06697

KEGG Drug

http://www.genome.jp/dbget-bin/www_bget?drug:D02483

BindingDB

http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50022886

PharmGKB

http://www.pharmgkb.org/drug/PA165111698

Wikipedia

http://en.wikipedia.org/wiki/Artemether

RxList

http://www.rxlist.com/coartem-drug.htm

Drugs.com

http://www.drugs.com/pro/coartem.html

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