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Pharmacokinetics an...
Pharmacokinetics and pharmacodynamics of oleylphosphocholine in a hamster model of visceral leishmaniasis
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- Fortin, Anny (författare)
- Dafra Pharma Res & Dev, Slachthuisstr 30-7, Turnhout, Belgium.;McGill Univ, Dept Biochem, 1650 Cedar Ave, Montreal, PQ, Canada.
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- Dorlo, Thomas P. C. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Univ Utrecht, Utrecht Inst Pharmaceut Sci, Div Pharmacoepidemiol & Clin Pharmacol, Utrecht, Netherlands.
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- Hendrickx, Sarah (författare)
- Univ Antwerp, Lab Microbiol Parasitol & Hyg LMPH, Univ Pl 1, Antwerp, Belgium.
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- Maes, Louis (författare)
- Univ Antwerp, Lab Microbiol Parasitol & Hyg LMPH, Univ Pl 1, Antwerp, Belgium.
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Dafra Pharma Res & Dev, Slachthuisstr 30-7, Turnhout, Belgium;McGill Univ, Dept Biochem, 1650 Cedar Ave, Montreal, PQ, Canada. Institutionen för farmaceutisk biovetenskap (creator_code:org_t)
- 2016-04-15
- 2016
- Engelska.
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Ingår i: Journal of Antimicrobial Chemotherapy. - : Oxford University Press (OUP). - 0305-7453 .- 1460-2091. ; 71:7, s. 1892-1898
- Relaterad länk:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- Objectives: This study evaluated the pharmacokinetic properties of oleylphosphocholine (OlPC) in hamsters following a single oral dose. Its prophylactic activity was tested to establish exposure-activity relationships, while a 5+5 day oral regimen at 20 mg/kg with long post-treatment follow-up was performed to assess its curative potential. Methods: Single oral doses of 20, 50 and 100 mg/kg were administered for pharmacokinetic analysis while a 100 mg/kg single oral dose was given on day 7, 4 or 1, or 4 h prior to infection in the prophylactic efficacy study. The animals were infected on day 0 with Leishmania infantum and the resulting parasite burdens were measured in target organs on day 21. In the curative model, treatment started on day 21 post-infection at 20 mg/kg for 5+5 days and amastigote burdens were determined in target organs either on day 42 [10 days after the end of treatment (dpt)] or day 72 (40 dpt). Results: OlPC showed elimination t(1/2) of similar to 50 h and dose-proportional exposure. The prophylactic action of OlPC was in agreement with model-simulated drug exposures, showing dose-dependent residual activity. Interestingly, the 100 mg/kg single dose administered 4 days before infection (day -4) still reduced the overall parasite burden by similar to 50%. In the curative model, >99% clearance of infection was observed at 10 dpt in all OlPC-treated animals and remained so at 40 dpt. Conclusions: This study reveals that total plasma exposure (AUC(t-infinity)) correlates well with the prophylactic and curative efficacy of OlPC in the L. infantum hamster model.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
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