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 th...
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ftdoajarticles:oai:doaj.org/article:9f27118e51254bf0a43ee17a6c7afe73 2023-05-15T15:16:34+02:00 Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. Thorsten Meyer Harald Sekljic Stefan Fuchs Heiko Bothe Dieter Schollmeyer Christian Miculka 2009-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000357 https://doaj.org/article/9f27118e51254bf0a43ee17a6c7afe73 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2614124?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000357 https://doaj.org/article/9f27118e51254bf0a43ee17a6c7afe73 PLoS Neglected Tropical Diseases, Vol 3, Iss 1, p e357 (2009) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2009 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000357 2022-12-31T01:58:21Z 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. METHODS AND FINDINGS: 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. FINDING: The schistosomicidal component alone is significantly less bitter than regular, racemic PZQ. CONCLUSION: 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLoS Neglected Tropical Diseases 3 1 e357 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Thorsten Meyer Harald Sekljic Stefan Fuchs Heiko Bothe Dieter Schollmeyer Christian Miculka Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
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. METHODS AND FINDINGS: 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. FINDING: The schistosomicidal component alone is significantly less bitter than regular, racemic PZQ. CONCLUSION: 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. |
format |
Article in Journal/Newspaper |
author |
Thorsten Meyer Harald Sekljic Stefan Fuchs Heiko Bothe Dieter Schollmeyer Christian Miculka |
author_facet |
Thorsten Meyer Harald Sekljic Stefan Fuchs Heiko Bothe Dieter Schollmeyer Christian Miculka |
author_sort |
Thorsten Meyer |
title |
Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. |
title_short |
Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. |
title_full |
Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. |
title_fullStr |
Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. |
title_full_unstemmed |
Taste, a new incentive to switch to (R)-praziquantel in schistosomiasis treatment. |
title_sort |
taste, a new incentive to switch to (r)-praziquantel in schistosomiasis treatment. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2009 |
url |
https://doi.org/10.1371/journal.pntd.0000357 https://doaj.org/article/9f27118e51254bf0a43ee17a6c7afe73 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 3, Iss 1, p e357 (2009) |
op_relation |
http://europepmc.org/articles/PMC2614124?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000357 https://doaj.org/article/9f27118e51254bf0a43ee17a6c7afe73 |
op_doi |
https://doi.org/10.1371/journal.pntd.0000357 |
container_title |
PLoS Neglected Tropical Diseases |
container_volume |
3 |
container_issue |
1 |
container_start_page |
e357 |
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1766346864642228224 |