Comparative Pharmacokinetic Studies of Dehydroemetine and Emetine in Guinea Pigs Using Spectrofluorometric and Radiometric Methods *

Increased Lifespan of Leukemic Mice Treated with Drugs Related to (–)-Emetine

“…The optimal dosage schedule for emetine however differed from that for methotrexate and injections on an intermittent basis (Q4D, day 1, 5, 9) were as effective as daily injec tions (QD, day 1-5 or QD, day 1-9) of smaller dosages. These results support the idea that the schedule dependency of the antileukemic activity of emetine may be a reflection of an unusually slow rate of urinary excre tion [12,40]. It should be noted however that the Q8D, day 1, 9 is less advantageous than the Q4D, day 1, 5, 9 schedule for prolonging the life span of the leukemic mice, which implies that there are limits, to the sus-tained storage of chemotherapeutically effective doses of emetine in the tissues [12,36,40,41].…”

“…The QD, day 1-9 schedule was the most effective of the three for treatment with ( ± )-2,3-dehydroemetine. This may be a reflection of the more rapid elimination of (±)-2,3-dehydroemetine from the animal compared to (-)-emetine (40).…”

“…However, in preliminary experiments on the effectiveness of (-)-emetine in prolonging the survival time of mice bearing L1210 tumors inoculated intracranially [Abbott, unpublished observations], it would appear that (-)-emetine does not substantially prolong the lifespan under these condi tions. This indicates that although (-)-emetine may cross the blood-brain barrier in guinea pigs [40] it does not penetrate the central nervous sys tem in chemotherapeutically effective doses in mice.…”

“…This is particularly pertinent since emetine crosses the blood-brain barrier [40] whereas folic acid an tagonists used in the chemotherapy of acute leukemia do not [3,10,11]. However, in preliminary experiments on the effectiveness of (-)-emetine in prolonging the survival time of mice bearing L1210 tumors inoculated intracranially [Abbott, unpublished observations], it would appear that (-)-emetine does not substantially prolong the lifespan under these condi tions.…”

“…(±)-2,3-Dehydroemetine which is thought to be as effective as (-)-emetine in the treatment of amebiasis [48] appears to be somewhat less active as an antileukemic agent in the mouse L1210 system (table II), but this may be related to its greater rate of ex cretion and elimination from storage sites in the tissues [40,41] and the conditions of testing which are more specifically optimal for (-)-emetine. However, it may well be that data obtained with ( ± )-2,3-dehydroemetine are also subject to species variation since there are indications that this derivative is selectively antileukemic under certain clinical conditions [1,2,49], (-)-2,3-Dehydroemetine is about twice as active (table IV) as the ra cemic ( ± )-2,3-dehvdroemetine [22], indicating that (+)-2,3-dehydroemetine ( fig.…”