The rat biliary metabolites of dihydroartemisinin, an antimalarial endoperoxide.
1997; American Society for Pharmacology and Experimental Therapeutics; Volume: 25; Issue: 10 Linguagem: Inglês
ISSN
1521-009X
AutoresMaggs Jl, Stephen F. Madden, Bishop Lp, O'Neill Pm, Park Bk,
Tópico(s)Pharmacogenetics and Drug Metabolism
Resumo[13-14C]Dihydroartemisinin was administered to male rats (35 μmol kg−1, iv). Within 0–1 hr and 0–5 hr of dosing, 34.8 ± 5.2% (mean ± SD, N = 6) and 48.4 ± 5.9% of the radiolabel, respectively, was recovered in bile. Only 1.1 ± 1.2% was recovered in bladder urine after 5 hr. The biliary metabolites were identified by LC/MS. The principal metabolite (21.1 ± 9.3% of dose) was the biologically inactive dihydroartemisinin (DHA) glucuronide. The other metabolites were products of reductive cleavage and rearrangement of the endoperoxide bridge, a process known to generate reactive radical intermediates and abolish antimalarial activity. They were desoxy-DHA (3.3 ± 2.0%) and its glucuronide (1.1 ± 1.0%), 3-hydroxydesoxy-DHA glucuronide (2.9 ± 1.8%), and the glucuronide of a ring-contracted tetrahydrofuran acetate isomer of DHA (6.9 ± 5.6%).
Referência(s)