Assessment of the effect of malaria infection on hepatic clearance of dihydroartemisinin using rat liver perfusions and microsomes

摘要

The clearance of dihydroartemisinin(DHA) in control and malaria-infected(MI) rats was investigated using the isolated perfused rat liver(IPRL) model and hepatic microsomal studies. In the recirculating IRPL, clearance of DHA was reduced from a mean (s.d.) of 8.2±1.8 ml min~-1 in Controls(n =8) to 6.0±1.0 ml min~-1 in MI(n=8; P<0.01). clearance in control livers was similar to The perfusion flow rate, suggesting a high hepatic extraction ratio of DHA. Single-pass IPRL studies in controls (n =8) showed that DHA bioavailability at 1.3, 8 and 38μM was 0.026±0.020, 0.043±0.025 and 0.14±0.06, respectively (P <0.001 for 8 μM vs 38μm).