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

Int J Pharm. 2011 Jul 29;414(1-2):260-6. doi: 10.1016/j.ijpharm.2011.05.003. Epub 2011 May 7.

Abstract

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 50.0mg/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.

MeSH terms

  • Absorption
  • Administration, Oral
  • Animals
  • Antimalarials / blood
  • Antimalarials / chemistry*
  • Antimalarials / pharmacokinetics*
  • Antimalarials / therapeutic use
  • Arachidonic Acid / chemistry
  • Artemisinins / blood
  • Artemisinins / chemistry*
  • Artemisinins / pharmacokinetics
  • Artemisinins / therapeutic use
  • Colloids / chemistry
  • Drug Carriers
  • Drug Compounding
  • Drug Delivery Systems / methods*
  • Excipients / chemistry
  • Glycerol / analogs & derivatives
  • Glycerol / chemistry
  • Malaria, Cerebral / drug therapy*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Particle Size
  • Plasmodium / drug effects*
  • Vitamins / chemistry
  • alpha-Tocopherol / chemistry

Substances

  • Antimalarials
  • Artemisinins
  • Colloids
  • Drug Carriers
  • Excipients
  • Vitamins
  • Arachidonic Acid
  • cremophor EL
  • artemisone
  • alpha-Tocopherol
  • Glycerol