Absorption of N-acetylcysteine in Healthy and Mycoplasma gallisepticum-Infected Chickens

Abstract

N-acetylcysteine (NAC) is widely used as a mucolytic agent in cases with inflammation of the lungs. NAC is applied in poultry with aflatoxin B1 intoxication as an antioxidant, but its pharmacokinetics are not known. The present study was conducted to characterize the population pharmacokinetics of orally administered NAC in broilers. It included 32 chickens, divided into four groups, treated with NAC at a dose rate of 100 mg/kg/day mixed with the feed: healthy broilers (n=6); chickens infected with Mycoplasma gallisepticum (n = 10); healthy broilers (n = 6); and diseased chickens (n = 10) treated with NAC and doxycycline (via drinking water, 20 mg/kg body weight (b.w.)). Plasma concentrations were analyzed by Liquid Chromatography –Mass Spectrometry (MS)/MS. NAC was absorbed after oral administration in all four groups of chickens. In healthy chickens treated solely with NAC, maximum plasma concentrations of 2.26 ± 0.91 µg mL−1 were achieved at 2.47 ± 0.45 h after dosing. The value of absorption half-life was 1.04 ± 0.53 h. The population pharmacokinetic analysis showed that dose adjustment of NAC is not required in M. gallisepticum-infected broilers or when it is combined with doxycycline.

LC–MS/MS determination of N‐acetyl‐l‐cysteine in chicken plasma

“…In the current investigation, the results about the recovery were in accordance with data reported for human plasma: 100.8-112.7% for a concentration range of 0.01-5 μg/ml (Lu et al, 2011). Similar values were found for chicken plasma: 98.51-101.88% for a concentration range of 0.25-10 μg/ml (Petkova & Milanova, 2021).…”

“…The LC-MS/MS method for quantitative analysis of NAC was validated according to the accepted criteria for accuracy, precision, sensitivity and recovery in the Guidelines on Bioanalytical Method Validation of European Medicine Agency (EMA, 2011). Our previous experiments showed that plasma levels of NAC after oral administration at a dose rate of 50 mg/kg/12 h with the feed were very low: 2.26 ± 0.91 μg/ml (Petkova & Milanova, 2021), around 10-fold lower in comparison with those in cats (Basu et al, 2012). In order to clarify the observed results, a classical pharmacokinetic investigation with intravenous and intraingluvial administration of NAC is required.…”

“…The previously published results for validation did not include determination of recovery (Petkova & Milanova, 2021).…”

“…Linearity for the wide range of concentrations used for NAC analytical procedure in cat plasma was not achieved in our study. Our previous work did not reveal the existing problem because of narrow range of validation, from 0.25 to 10 μg/ml (Petkova & Milanova, 2021). The LC-MS/MS method was developed by application of the split calibration curve approach because linearity was not observed within the total range of the concentrations from 0.05 to 100 μg/ml.…”

“…Only a single pilot study reveals the pharmacokinetics of NAC after multiple administrations in broilers (Petkova & Milanova, 2021). The increased interest in this drug for application in chickens requires good knowledge of its pharmacokinetics to suggest a rational dose on this basis.…”