Bioavailability, distribution and depletion of monensin in chickens

Abstract

The pharmacokinetics of monensin including apparent volume of distribution, total body clearance, systemic bioavailability, partition coefficients and tissue residues were determined in chickens. The drug was given by intravenous injection in the left wing vein at the dose of 0.46 mg/kg and by intracrop administration at the dose of 4 mg/kg according to a destructive sampling. The pharmacokinetic variables were compared after noncompartmental, naïve averaged, naïve pooled and nonlinear mixed-effects modelling analyses. Partition coefficients and tissue residues were determined after a treatment with feed additives (125 mg/kg of feed) of 33 days. The clearance, volume of distribution and bioavailabilty were approximately 2.2 L/h/kg, approximately 9 L/kg and approximately 30% respectively except with nonlinear mixed effects models that presented values of 1.77 L/h/kg, 14.05 L/kg and 11.36% respectively. Tissue/plasma partition coefficients were estimated to 0.83, 3.39 and 0.51 for liver, fat and thigh muscle respectively. Monensin residues after treatment were not detected 6 h after withdrawal except for fat where monensin was still quantifiable 12 h after. Pharmacokinetic variables seem to be inaccurate when assessed with non linear mixed-effects modelling associated to destructive sampling in chickens. Values varied slightly with noncompartmental, naïve averaged and naïve pooled analyses. The absorption, elimination and partition parameters will be incorporated into a physiologically based pharmacokinetic model and the depletion study will be used to test the ability of this model to describe monensin residues in edible tissues under different dosage regimens.

Comparison of the oral bioavailability and tissue disposition of monensin and salinomycin in chickens and turkeys

“…The one‐point‐per‐animal design is not, however, suitable to get an accurate determination of individual parameters of each animal. T 1 /2 of monensin in chickens (Henri et al. , 2009) was two to three times that of monensin in turkeys, which suggests that the withdrawal time for monensin should be shorter in turkeys than in chickens.…”

Forty years of monensin for the control of coccidiosis in poultry

“…Bioavailability, distribution, and depletion have been studied in chickens by injection and intracrop administration (Henri et al, 2009). Residues were not detected 6 h after withdrawal except in fat where the drug was detectable 12 h later.…”

A physiologically based pharmacokinetic model for chickens exposed to feed supplemented with monensin during their lifetime

“…The first optimization procedure (with a ‘constant weight’ model) correctly fitted the plasma concentration–time data after a single oral dose of monensin in solution. The predicted curve (data not shown) was close to that attained previously using classical compartmental modelling (Henri et al ., ). The fabs (for monensin in solution), K CROP , P RICHLY and P POORLY parameters were thus estimated.…”

“…Each compartment was described by its volume ( V X ), its perfusion rate (Qc X ) and its tissue/plasma partition coefficient ( P X ). Partition coefficients were taken from the literature (Henri et al ., ) except for P RICHLY and P POORLY which were estimated according to this model (see below). This description was the same for all compartments except for plasma for which the volume was corrected with the haematocrit H (Yang et al ., 2014b):where FracV BLOOD is the fraction of volume representing blood.…”

“…These studies estimate the bioavailability of monensin (in solution) in chickens to be between 11 and 31%. This estimation (even if it is imprecise) has been confirmed by a more recent study involving high‐performance liquid chromatography coupled with tandem mass spectrometry (HPLC‐MS/MS) (Henri et al ., ). This HPLC‐MS/MS study also calculated other oral absorption parameters and demonstrated a lag time.…”