Absorption of the novel artemisinin derivatives artemisone and artemiside: Potential application of Pheroid™ technology

• Published in: International journal of pharmaceutics Vol. 414; no. 1; pp. 260 - 266
• Main Authors: Steyn, J. Dewald, Wiesner, Lubbe, du Plessis, Lissinda H., Grobler, Anne F., Smith, Peter J., Chan, Wing-Chi, Haynes, Richard K., Kotzé, Awie F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 29-07-2011; Elsevier
• Subjects: Absorption; administered dose; Administration, Oral; alpha-Tocopherol - chemistry; Animals; Antimalarials - blood; Antimalarials - chemistry; Antimalarials - pharmacokinetics; Antimalarials - therapeutic use; Arachidonic Acid - chemistry; Artemiside; artemisinin; Artemisinins - blood; Artemisinins - chemistry; Artemisinins - pharmacokinetics; Artemisinins - therapeutic use; Artemisone; bioavailability; Biological and medical sciences; blood; body weight; cerebral malaria; Colloids - chemistry; Drug Carriers; Drug Compounding; Drug Delivery Systems - methods; drugs; Excipients - chemistry; General pharmacology; Glycerol - analogs & derivatives; Glycerol - chemistry; Malaria; Malaria, Cerebral - drug therapy; Male; Medical sciences; Mice; Mice, Inbred C57BL; oral administration; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacokinetic analysis; pharmacokinetics; Pharmacology. Drug treatments; Pheroid™ technology; Plasmodium - drug effects; solubility; Vitamins - chemistry; Pheroid™ technology; Artemisone; Malaria; Pharmacokinetic analysis; Artemiside; Antimalarial; Protozoal disease; Pharmaceutical technology; Artemisinin; Parasitosis; Infection; Absorption; Parasiticide; Pharmacokinetics
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2011.05.003

Artemisinins have low aqueous solubility that results in poor and erratic absorption upon oral administration. The poor solubility and erratic absorption usually translate to low bioavailability. Artemisinin-based monotherapy and combination therapies are essential for the management and treatment of uncomplicated as well as cerebral malaria. Artemisone and artemiside are novel artemisinin derivatives that have very good antimalarial activities. Pheroid™ technology is a patented drug delivery system which has the ability to entrap, transport and deliver pharmacologically active compounds. Pharmacokinetic models were constructed for artemisone and artemiside in Pheroid™ vesicle formulations. The compounds were administered at a dose of 50.0
mg/kg bodyweight to C57 BL/6 mice via an oral gavage tube and blood samples were collected by means of tail-bleeding. Drug concentrations in the samples were determined using an LC/MS/MS method. There was 4.57 times more artemisone in the blood when the drug was entrapped in Pheroid™ vesicles in comparison to the drug only formulation (
p
<
0.0001). The absorption of artemiside was not dramatically enhanced by the Pheroid™ delivery system.