Biomaterial Database

Antimalarial activity of dihydroartemisinin derivatives by transdermal application. 1994

A J Lin, and A L Ager, and D L Klayman

Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Washington, District of Columbia.

In addition to artelinic acid, which was demonstrated previously to possess good prophylactic as well as curative antimalarial activity against Plasmodium berghei by transdermal administration, seven artemisinin derivatives in a gel formulation were assessed for their antimalarial activities in this study. Artemisinin, the parent compound of the series, showed moderate prophylactic but poor curative activity. Although methyl artelinate was more active against P. berghei than artelinic acid and sodium artelinate by subcutaneous injection, its transdermal curative and prophylactic activity was only comparable with or weaker than that of artelinic acid. Conversely, both dihydroartemisinin trimethylsilyl ether and dehydrodihydroartemisinin showed weaker antimalarial activity than artelinic acid by the subcutaneous route, yet exhibited comparable activity by transdermal administration. Artemether, a prodrug of dihydroartemisinin, is as effective as the parent dihydroartemisinin, and both compounds were the most potent agents among the compounds studied, with total prophylactic and curative doses of 30 mg/kg and 60 mg/kg, respectively. Complete absorption of dihydroartemisinin appears to occur within 5 min after application. In general, we found that the prophylactic dose is about half that of the curative dose under the protocols used in this study. This novel drug delivery system may be an easy and safe way to administer artemisinin-type antimalarials and also a good alternative dosage form for active compounds with solubility problems.

UI	MeSH Term	Description	Entries
D008288	Malaria	A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.	Marsh Fever,Plasmodium Infections,Remittent Fever,Infections, Plasmodium,Paludism,Fever, Marsh,Fever, Remittent,Infection, Plasmodium,Plasmodium Infection
D010962	Plasmodium berghei	A protozoan parasite of rodents transmitted by the mosquito Anopheles dureni.	Plasmodium bergheus,berghei, Plasmodium
D005782	Gels	Colloids with a solid continuous phase and liquid as the dispersed phase; gels may be unstable when, due to temperature or other cause, the solid phase liquefies; the resulting colloid is called a sol.
D000077549	Artemether	An artemisinin derivative that is used in the treatment of MALARIA.	Artemether, (3R-(3alpha,5abeta,6alpha,8abeta,9alpha,10beta,12beta,12aR))-isomer,Artemether, (3R-(3alpha,5abeta,6beta,8aalpha,9alpha,10beta,12beta,12aR))-isomer,Artemether, (3R-(3alpha,5abeta,6beta,8abeta,9alpha,10alpha,12beta,12aR*))-isomer,Artenam,O-Methyldihydroartemisinine,alpha-Artemether,beta-Arthemeter,O Methyldihydroartemisinine,alpha Artemether,beta Arthemeter
D000279	Administration, Cutaneous	The application of suitable drug dosage forms to the skin for either local or systemic effects.	Cutaneous Drug Administration,Dermal Drug Administration,Drug Administration, Dermal,Percutaneous Administration,Skin Drug Administration,Transcutaneous Administration,Transdermal Administration,Administration, Dermal,Administration, Transcutaneous,Administration, Transdermal,Cutaneous Administration,Cutaneous Administration, Drug,Dermal Administration,Drug Administration, Cutaneous,Skin Administration, Drug,Administration, Cutaneous Drug,Administration, Dermal Drug,Administration, Percutaneous,Administrations, Cutaneous,Administrations, Cutaneous Drug,Administrations, Dermal,Administrations, Dermal Drug,Administrations, Percutaneous,Administrations, Transcutaneous,Administrations, Transdermal,Cutaneous Administrations,Cutaneous Administrations, Drug,Cutaneous Drug Administrations,Dermal Administrations,Dermal Drug Administrations,Drug Administrations, Cutaneous,Drug Administrations, Dermal,Drug Skin Administrations,Percutaneous Administrations,Skin Administrations, Drug,Skin Drug Administrations,Transcutaneous Administrations,Transdermal Administrations
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000962	Antimalarials	Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585)	Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D012717	Sesquiterpenes	Fifteen-carbon compounds formed from three isoprenoid units with general formula C15H24.	Farnesanes,Farnesene,Farnesenes,Sesquiterpene,Sesquiterpene Derivatives,Sesquiterpenoid,Sesquiterpenoids,Derivatives, Sesquiterpene
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus