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

ABSTRACT

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 10 mg/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,v) = X(0 )(8.4191 × 10(-4) × e(-0.2371t) + 1.2788 × 10(-5) × e(-0.0069t)) after i.v. and C(p.o) = X(0) (-8.4964 × 10(-4) × e(-0.5840t) + 8.4195 × e(-0.2371t) + 7.6869 × 10(-6) × e(-0.0069t)) after p.o. Monte Carlo simulation showed that T(>MIC) was more than 24 h when a single daily dosage at 13.5 mg/kg BW in pigs was administrated by p.o., and MIC was 0.031 mg/L. It was concluded that the current dosage regimen at 10-12 mg/kg BW led to valnemulin underexposure if the MIC was more than 0.031 mg/L and could increase the risk of treatment failure and/or drug resistance.