Accession Number : ADA319697

Title :   Support of Study Entitled, 'Metabolism and Pharmacokinetics of Dihydroartemisinin' and 'In Vitro and In Vivo Metabolism of Sodium Artelinate and DQHS in Rats and Humans'.

Descriptive Note : Midterm rept. 1 Jan 94-30 Sep 96,

Corporate Author : IDOWU (OLUTOSIN R) SILVER SPRING MD

Personal Author(s) : Idowu, Olutosin R.

PDF Url : ADA319697

Report Date : OCT 1996

Pagination or Media Count : 59

Abstract : Identification of the metabolites of DQHS and other artemisinin analogues has been problematic because of the unavailability of standards of the putative metabolites. The following report presents our attempts to circumvent this problem through a combination of mass spectrometry and derivatization of DQHS. The metabolism of dinydroqinghaosu (DQHS) (dihydroartemisinin) in rat liver microsomes and the isolated perfused rat liver was studied. The metabolites were identified by high performance liquid chromatography/thermospray (TSP) mass spectrometry. The metabolism of DQHS was found to involve C-hydroxylation at the 2-, 3-, 9-, or 14-position. Deoxygenation of the endoperoxide function together with C-hydroxylation gave rise to different isomers of hydroxy deoxydihydroqinghaosu (hydroxy deoxyDQHS), the prevalent metabolites of DQHS. DQHS also apparently underwent enzymatic oxidation to isomers of both hydroxy deoxyqinghaosu and dihydroxy deoxyQHS.

Descriptors :   *RATS, *HUMANS, *METABOLISM, *IN VITRO ANALYSIS, *PHARMACOKINETICS, *IN VIVO ANALYSIS, QUANTITATIVE ANALYSIS, ENZYMES, ISOMERS, OXIDATION, LIQUID CHROMATOGRAPHY, LABORATORY PROCEDURES, LIVER, METABOLITES, ANTIMALARIALS, OXIDATION REDUCTION REACTIONS, MICROSOMES, MASS SPECTROMETRY, SODIUM COMPOUNDS, LACTONES.

Subject Categories : Biochemistry
      Medicine and Medical Research
      Pharmacology
      Anatomy and Physiology
      Physical Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE