4.1 Article

Dosage assessment of valnemulin in pigs based on population pharmacokinetic and Monte Carlo simulation

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出版社

WILEY
DOI: 10.1111/jvp.12199

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资金

  1. National Science Fund for Distinguished Young Scholars of China [31125026]
  2. National Natural Science Foundation of China [30972219]
  3. Natural Science Foundation of Guangdong Province [10451064201005477]
  4. Science and Technology Program of Guangzhou [2012J4300053]
  5. Key Project of DEGP [CXZD1118]
  6. Guangdong Provincial Key Laboratory of Prevention and Control for Severe Clinical Animal Diseases [2013A061401013]

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To estimate the valnemulin pharmacokinetic profile in a swine population and to assess a dosage regimen for increasing the likelihood of optimization. This study was, respectively, performed in 22 sows culled by p.o. administration and in 80 growing-finishing pigs by i.v. administration at a single dose of 10mg/kg to develop a population pharmacokinetic model and Monte Carlo simulation. The relationships among the plasma concentration, dose, and time of valnemulin in pigs were illustrated as C-i,C-v=X-0(8.4191x10(-4) x e(-0.2371t) + 1.2788 x 10(-5) x e(-0.0069t)) after i.v. and C-p.o = X-0(-8.4964 x 10(-4) x e(-0.5840t) + 8.4195 x e(-0.2371t) +7.6869x10(-6)xe(-0.0069t)) after p.o. Monte Carlo simulation showed that T->MIC was more than 24h when a single daily dosage at 13.5mg/kg BW in pigs was administrated by p.o., and MIC was 0.031mg/L. It was concluded that the current dosage regimen at 10-12mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031mg/L and could increase the risk of treatment failure and/or drug resistance.

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