The effect of the Pheroid delivery system on the in vitro metabolism and in vivo pharmacokinetics of artemisone
| Autor: | Anne Grobler, Collen Masimirembwa, Paul A. Steenkamp, Richard K. Haynes, Lizette Grobler, H.S. Steyn, Roslyn Thelingwani |
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| Přispěvatelé: | 22966390 - Haynes, Richard Kingston, 10176527 - Steyn, Hendrik Stefanus, 11008857 - Grobler, Anne Frederica, 13065513 - Grobler, Lizette |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Artemisone
Biological Availability Pharmacology Toxicology Drug Delivery Systems Tandem Mass Spectrometry Microsomes Area under curve Chlorocebus aethiops Medicine Animals Humans Pharmacokinetics Intestinal Mucosa Technology innovation business.industry In vitro metabolism General Medicine Artemisinins Joint research Intestines Monkey Liver metabolism Area Under Curve Models Animal Linear Models Microsomes Liver Clearance Delivery system business Pheroid In vivo pharmacokinetics Chromatography Liquid |
| ISSN: | 1742-5255 |
| DOI: | 10.1517/17425255.2014.885503 |
| Popis: | Objectives: 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 http://dx.doi.org/10.1517/17425255.2014.885503 http://www.tandfonline.com/loi/iemt20#.VjiobytpETY South African Technology Innovation Agency (TIA), the Swiss South African Joint Research Project Initiative and the North-West University |
| Databáze: | OpenAIRE |
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