The effect of praziquantel on Hymenolepis diminuta in vitro

Qualitative observations were made on Hymenolepis diminuta, H. microstoma, H. nana and pre-adult Echinococcus multilocularis in vitro. A dose as low as 0.0001 microgram praziquantel/ml affects the tapeworms, while concentrations of 0.01 - 0.1 and 1-10 microgram/ml cause contraction and paralysis in the contracted state within 10 min and 10-30 s, respectively. The in vitro effects of praziquantel on Hymenolepis diminuta have been studied using anaerobic and aerobic incubations and media containing or lacking glucose. Praziquantel inhibits glucose up-take by half at a concentration of 0.1 microgram/ml, both under anaerobic and aerobic conditions. The stimulation of lactate release was most marked in the absence of glucose. A doubling of the amount of lactate released during anaerobic incubation in the presence of glucose was achieved in 0.1 microgram/ml, while 0.01 microgram/ml had the same effect in the absence of glucose. Under aerobic conditions and in the absence of glucose, 0.1 microgram/ml doubled the amount of lactate released while 3 and 10 microgram/ml were without effect in the presence of glucose. Praziquantel increases the total amount of excreted acidic metabolites only in the absence of glucose. The oxygen consumption of H. diminuta was unaffected by praziquantel at a concentration of 10 microgram/ml. Worms treated in their host and then incubated display the same changes as worms treated in vitro. Praziquantel causes an efflux of glucose and alpha-amino-N from the worm into the medium. This impairment of tegumental integrity and the inhibition of glucose up-take and the stimulation of lactate release are reversible after a 15 min incubation in praziquantel solution. Discussion of pharmacokinetic data indicates, that in the in vivo situation, effective concentrations of praziquantel prevail for much longer. Mechanisms that might explain the observed effects are discussed.