title: The effect of the Pheroid delivery system on the in vitro metabolism and in vivo pharmacokinetics of artemisone.
abstract: OBJECTIVE
  The objectives were to determine the pharmacokinetics (PK) of artemisone and artemisone formulated in the Pheroid® drug delivery system in primates and to establish whether the formulation affects the in vitro metabolism of artemisone in human and monkey liver and intestinal microsomes.
  
  
  METHODS
  For the PK study, a single oral dose of artemisone was administered to vervet monkeys using a crossover design. Plasma samples were analyzed by means of liquid chromatography-tandem mass spectrometry. For the in vitro metabolism study, clearance was determined using microsomes and recombinant CYP3A4 enzymes, and samples were analyzed by means of ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry.
  
  
  RESULTS
  Artemisone and M1 plasma levels were unexpectedly low compared to those previously recorded in rodents and humans. The in vitro intrinsic clearance (CLint) of the reference formulation with monkey liver microsomes was much higher (1359.33 ± 103.24 vs 178.86 ± 23.42) than that of human liver microsomes. The in vitro data suggest that microsomal metabolism of artemisone is inhibited by the Pheroid delivery system.
  
  
  CONCLUSIONS
  The in vivo results obtained in this study indicate that the Pheroid delivery system improves the PK profile of artemisone. The in vitro results indicate that microsomal metabolism of artemisone is inhibited by the Pheroid delivery system.
authors: North-West University, Faculty of Health Sciences, DST/NWU Preclinical Drug Development Platform , Potchefstroom , South Africa +27 18 299 2281, +27 18 299 4467 ; +27 18 285 2233 ; 13065513@nwu.ac.za ; Anne.Grobler@nwu.ac.za.
authors: Lizette
authors: L
authors: Grobler
authors: Anne
authors: A
authors: Grobler
authors: Richard
authors: R
authors: Haynes
authors: Collen
authors: C
authors: Masimirembwa
authors: Roslyn
authors: R
authors: Thelingwani
authors: Paul
authors: P
authors: Steenkamp
authors: Hendrik Stefanus
authors: HS
authors: Steyn
mesh_terms: D000818:Animals; D019540:Area Under Curve; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002522:Chlorocebus aethiops; D002853:Chromatography, Liquid; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D016014:Linear Models; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D053719:Tandem Mass Spectrometry
chemical_list: D037621:Artemisinins; C514498:artemisone