Effects of artemisinin, artemether, and arteether on the pharmacokinetics of phenytoin

The aim of the study was to determine the effect of artemisinin, artemether, and arteether on the pharmacokinetics of phenytoin in rabbits. In a cross-over study, phenytoin (30 mg/kg/day, o.s.) was given daily for 7 days. On day 7, blood samples were taken at various time intervals between 0 and 24 h. In the artemisinin group, phenytoin was administered for 7 days. On day 8, artemisinin alone (82 mg/kg) was administered, followed by artemisinin (41 mg/kg) along with phenytoin (30 mg/kg/day) for the next 2 days, and blood samples were drawn at various time intervals. For the artemether group, artemether (10 mg/kg, i.m.) was given on day 8, followed by artemether (5 mg/kg, i.m.) for 2 days. For the arteether group, arteether (10 mg/kg, i.m.) was given from day 8 for 3 days. Plasma phenytoin levels were assayed by HPLC, and pharmacokinetic parameters were calculated. In the artemisinin group, there was a significant decrease in t(1/2) a of phenytoin. In the artemether group, t(1/2) el decreased compared to that of controls. In the arteether group, no significant change was observed in the pharmacokinetic parameters. These results suggest that artemisinin compounds alter the pharmacokinetics of phenytoin. Confirmation of these results in human studies will warrant changes in phenytoin dose or frequency, when either of these antimalarials is coadministered with it.