Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment.
BACKGROUND
Praziquantel (PZQ) is the drug compound of choice in the control and treatment of schistosomiasis. PZQ is administered as a racemate, i. e. 1ratio1 mixture of enantiomers. The schistosomicidal activity arises from one PZQ-enantiomer, whereas the other enantiomer does not contribute to the activity. The WHO's Special Programme for Research and Training in Tropical Diseases (TDR) has assigned the low-cost preparation of pure schistosomicidal (-)-PZQ a key priority for future R&D on PZQ, but so far this transition has not happened. PZQ has two major administration drawbacks, the first being the high dose needed, and its well documented bitter and disgusting taste. Attempts of taste-masking by low-cost means have not been successful. We hypothesized that the non-schistosomicidal component in PZQ would be the main contributor to the unpleasant taste of the drug. If the hypothesis was confirmed, the two major administration drawbacks of PZQ, the high dose needed and its bitter taste, could be addressed in one go by removing the component contributing to the bitter taste.


RESULTS
PZQ was separated into its schistosomicidal and the non-schistosomicidal component, the absolute stereochemical configuration of (-)-PZQ was determined to be (R)-PZQ by X-ray crystallography, and the extent of bitterness was determined for regular racemic PZQ and the schistosomicidal component in a taste study in humans.


RESULTS
The schistosomicidal component alone is significantly less bitter than regular, racemic PZQ.


CONCLUSIONS
Our hypothesis is confirmed. We propose to use only the pure schistosomicidal component of PZQ, offering the advantage of halving the dose and expectedly improving the compliance due to the removal of the bitter taste. Therefore, (R)-PZQ should be specifically suitable for the treatment of school-age children against schistosomiasis. With this finding, we would like to offer an additional incentive to the TDR's recommendation to switch to the pure schistosomicidal (R)-PZQ.
Meyer
Thorsten
T
Intervet Innovation GmbH, Schwabenheim, Germany.
Sekljic
Harald
H
Fuchs
Stefan
S
Bothe
Heiko
H
Schollmeyer
Dieter
D
Miculka
Christian
C
D002648:Child; D018360:Crystallography, X-Ray; D006801:Humans; D015394:Molecular Structure; D011223:Praziquantel / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry*; D012552:Schistosomiasis / Q000188:drug therapy*; D012556:Schistosomicides / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry*; D013237:Stereoisomerism; D013649:Taste
D012556:Schistosomicides; D011223:Praziquantel