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Praziquantel, a new broad-spectrum antischistosomal agent

  • Praziquantel-Data On The Efficacy Against Schistosoma Mansoni, S. Haematobium, And S. Japonicum In Experimentally Infected Animals
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Summary

Praziquantel, (2-cyclohexylcarbonyl)-1,2,3,6,7,11b-hexa-hydro-2H pyrazino[2,1a]isoquinolin-4-one, belongs to a new series of antischistosomal compounds. The results of a detailed study of the efficacy of praziquantel on Schistosoma mansoni in mice, Mastomys and Syrian hamsters are described.

Praziquantel is effective after oral and all parenteral routes of administration tested. The amount of praziquantel required to achieve parasite reductions of at least 95% depends on the host species and on the routes and schedules of administration. Total doses range from 200–1,000 mg/kg in mice and from 100–500 mg/kg for Mastomys and hamsters.

In all three species, splitting of the total dose into 3 or more fractional doses given within 1 day approximately doubles the efficacy over that achieved after a single oral administration of the same total dose. A single subcutaneous dose is only slightly more effective, whilst a single intramuscular injection in olive oil is about twice as effective as a single oral administration.

Praziquantel is very effective against the invading stages and slightly less against schistosomules up to an age of 7 days. It is less effective against 2- to 4-week-old juveniles, but is effective again against 5-week-old and older schistosomes.

Praziquantel is equally effective against both sexes of S. mansoni. It is less effective against unpaired and therefore juvenile female worms, but fully effective against single male worms.

The efficacy of praziquantel on S. mansoni in mice is not influenced by the strain or the sex of the host, the worm burden or the age of the infection.

Considering all data available, praziquantel promises to be a very potent antischistosomal drug.

Zusammenfassung

Praziquantel, (2-Cyclohexylcarbonyl)-1,2,3,6,7,11b-hexa-hydro-2H-pyrazino[2,1a]isochinolin-4-on), gehört zu einer neuen Reihe von Schistosomenmitteln. Die Arbeit beschreibt eingehend Versuche zur Wirksamkeit von Praziquantel gegen Schistosoma mansoni in Maus, Mastomys und Goldhamster.

Praziquantel ist nach oraler und allen geprüften parenteralen Verabreichungsweisen wirksam. Die für eine 95%ige Parasitenreduktion benötigte Dosis hängt von der Art des Wirtes und der Applikationsweise ab. Sie beträgt 200–1,000 mg/kg bei der Maus und 100–500 mg/kg bei Mastomys und Goldhamstern.

Bei allen drei Wirten bewirkt die Aufteilung der Gesamtdosis auf mehrere im Laufe eines Tages gegebene Teildosen eine Verdoppelung der Wirksamkeit im Vergleich zur einmaligen oralen Gabe. Die einmalige subcutane Gabe ist nur geringfügig wirksamer als die einmalige orale Gabe, aber eine intramuskuläre Gabe in Olivenöl ist wiederum etwa doppelt so wirksam.

Praziquantel ist gegen die jüngsten Schistosomulae in der Haut hoch wirksam und etwas geringer wirksam gegen Schistosomulae bis zum Alter von 7 Tagen. Gegen 2–4 Wochen alte Jugendliche ist es weniger wirksam. Ab einem Alter von 5 Wochen werden S. mansoni wieder voll erfaßt.

Praziquantel ist gegen gepaarte S. mansoni beider Geschlechter und gegen ungepaarte Männchen gleich gut wirksam. Gegen ungepaarte und daher juvenile Weibchen ist es weniger wirksam.

Die Wirksamkeit von Praziquantel gegen S. mansoni wird nicht beeinflußt von Stamm oder Geschlecht des Wirtstieres und auch nicht von der Anzahl oder dem Alter der Parasiten.

Unter Berücksichtigung aller Ergebnisse verspricht Praziquantel ein hoch wirksames Schistosomenmittel zu sein.

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  1. Institute of Chemotherapy, Bayer AG, Wuppertal, Germany

    R. Gönnert & P. Andrews

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  2. P. Andrews
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Gönnert, R., Andrews, P. Praziquantel, a new broad-spectrum antischistosomal agent. Z. F. Parasitenkunde 52, 129–150 (1977). https://doi.org/10.1007/BF00389899

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