dc.contributor.author |
Tubbs, Lincoln |
en |
dc.date.accessioned |
2009-10-15T23:48:49Z |
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dc.date.available |
2009-10-15T23:48:49Z |
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dc.date.issued |
2007 |
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dc.identifier.citation |
Thesis (PhD--Biological Sciences)--University of Auckland, 2007 |
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dc.identifier.uri |
http://hdl.handle.net/2292/5363 |
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dc.description |
Full text is available to authenticated members of The University of Auckland only. |
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dc.description.abstract |
Disease management strategies are crucial to maintain the welfare of animals in aquaculture. A fundamental aspect of these strategies is the ability to deliver effective treatments in the most efficient manner possible. Disease due to infection with monogenean parasites is a cause of significant morbidity and mortality in the aquaculture of Seriola species globally. In New Zealand monogeneans are problematic in the culture of kingfish S. Ialandi, hence there is a need to develop a management strategy for these parasites that includes an effective treatment. The present work used a pharmacological approach to evaluate the metabolism, pharmacokinetics and concentration-effect relationship of praziquantel (PZQ) to assist the development of monogenean treatments for this industry. As with mammals, the primary phase one metabolites formed in kingfish during the biotransformation of orally administered PZQ included mono- and di-hydroxylated species. Importantly, enteral absorption of PZQ in kingfish was rapid after oral administration, reaching a peak (Tmax) 1 h and 1.5 h post-administration in plasma and skin respectively. The maximum concentration (Cmax) achieved in plasma following a 40 mg.kg-1 dose was 12.73 lig. mr1 after oral administration compared with 20.30 lig.m1-1 given intravenously. Absorption was modified with food, however, and T. in skin and plasma occurred 6 h post-administration when the drug was administered in a medicated diet; bioavailability (AUC0.24) of the oral dose was slightly improved when the drug was administered with food rather than in solution and resulted in plasma PZQ concentrations that were 56.8% of an intravenous dose compared with 50.8% respectively. Drug concentrations in the skin of kingfish were approximately 40-50% of the plasma values, with a similar bioavailability. Mild differences in temperature appeared to have no effect on bioavailability; no difference in plasma AUC0_24h was observed when an oral bolus dose was administered at 17°C or 22°C. Interestingly, a three-fold increase in the administered dose, from 50 mg.kg"1 to 150 mg.kg-1 only led to approximately 50% higher maximum PZQ concentrations in kingfish plasma (9.06 gg.mr1 compared with 15.80 ggsnr1). The same trend was seen on subsequent days when the drug was administered at 24 h intervals. In skin, however, Cmax was significantly higher; PZQ concentrations achieved following a 150mg.kg-1 dosage at 24 h intervals were on average 2.4 times higher than after a 50mg.kg"1dosage in this tissue (4.19 fig.g-1 with the low dose compared with 9.39 gg.g-1). Only minor accumulation of residual drug occurred following multiple dose administration at 24 h intervals, and only at the lower of these two doses. A monogenean culture system was developed to evaluate the dose-concentration-effect relationship between PZQ and the kingfish monogenean Benedenia seriolae as well as determine the potential effectiveness of alternative anthelmintics. This in vitro system revealed that exposure to revealed that exposure to concentrations of 13.6 p,g.g-1 PZQ for up to 5 h were required to remove attached B. seriolae from kingfish skin. Furthermore, this system demonstrated that a compound with demonstrated efficacy against B. seriolae in an in vitro immersion situation, caprylic acid, was unable to induce an effective response at the same concentration when the parasite was separated from the compound by a skin barrier. The combination of pharmacokinetic and pharmacodynamic data in the present study revealed inefficiencies with existing oral PZQ dosing regimens for kingfish monogenean therapy; these data were used to suggest mechanisms by which dosing regimens may be modified to improve the efficiency of monogenean treatment in kingfish with this drug. Although a kingfish-monogenean model was examined in this study, this type of approach to treatment development may be applicable to wider disease management strategies for aquaculture. |
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dc.language |
en |
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dc.publisher |
ResearchSpace@Auckland |
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dc.relation.ispartof |
PhD Thesis - University of Auckland |
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dc.relation.isreferencedby |
UoA99176751214002091 |
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dc.rights |
Restricted Item. Available to authenticated members of The University of Auckland. |
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dc.rights |
Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. |
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dc.rights.uri |
https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm |
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dc.title |
Pharmacology of praziquantel for parasite management strategies in kingfish aquaculture |
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dc.type |
Thesis |
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thesis.degree.discipline |
Biological Sciences |
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thesis.degree.grantor |
The University of Auckland |
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thesis.degree.level |
Doctoral |
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thesis.degree.name |
PhD |
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dc.rights.holder |
Copyright: The author |
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dc.identifier.wikidata |
Q112871002 |
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