Tissue distribution of bromhexine hydrochloride in broiler chickens following oral administration via drinking water
Fang Yang1, Jun Liang2, Ming-Hui Duan1
1Laboratory of Veterinary Drug Development and Evaluation, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471023, China.
This study aimed to investigate the tissue distribution of bromhexine hydrochloride in broiler chickens following oral administration via drinking water. Thirty-six healthy broilers were acclimated for one week, then 30 birds received drinking water containing 3.3 mg/L bromhexine hydrochloride for 10 consecutive days. Plasma and tissue samples, including muscle, liver, kidney, skin + fat, trachea, and lung, were collected at multiple time points after drug withdrawal for quantification using a validated UPLC-MS/MS method. Concentration analysis revealed that bromhexine hydrochloride was limited distributed in broilers, and rapidly eliminated from plasma and most tissues, with the longest half-life (t1/2λZ) observed in skin + fat (11.182 days), followed by liver (5.913 days), kidney (3.364 days), and muscle (3.129 days). In contrast, drug concentrations in the therapeutic target tissues were low and declined quickly, possibly due to limited systemic distribution and local clearance mechanisms. Despite the prolonged retention in lipid-rich tissues (skin-on fat), residue levels remained low across all tissues, with a maximum average concentration of only 17.79 ng/g in skin + fat. Given these findings and the broad safety profile of bromhexine hydrochloride-classified by the European Medicines Agency (EMA) as not requiring a maximum residue limit (MRL)-establishing a withdrawal period for this compound under the current dosing regimen appears unnecessary. These results provide valuable data to inform the safe and effective use of bromhexine hydrochloride in poultry production.
This study aimed to investigate the tissue distribution of bromhexine hydrochloride in broiler chickens following oral administration via drinking water. Thirty-six healthy broilers were acclimated for one week, then 30 birds received drinking water containing 3.3 mg/L bromhexine hydrochloride for 10 consecutive days. Plasma and tissue samples, including muscle, liver, kidney, skin + fat, trachea, and lung, were collected at multiple time points after drug withdrawal for quantification using a validated UPLC-MS/MS method. Concentration analysis revealed that bromhexine hydrochloride was limited distributed in broilers, and rapidly eliminated from plasma and most tissues, with the longest half-life (t1/2λZ) observed in skin + fat (11.182 days), followed by liver (5.913 days), kidney (3.364 days), and muscle (3.129 days). In contrast, drug concentrations in the therapeutic target tissues were low and declined quickly, possibly due to limited systemic distribution and local clearance mechanisms. Despite the prolonged retention in lipid-rich tissues (skin-on fat), residue levels remained low across all tissues, with a maximum average concentration of only 17.79 ng/g in skin + fat. Given these findings and the broad safety profile of bromhexine hydrochloride-classified by the European Medicines Agency (EMA) as not requiring a maximum residue limit (MRL)-establishing a withdrawal period for this compound under the current dosing regimen appears unnecessary. These results provide valuable data to inform the safe and effective use of bromhexine hydrochloride in poultry production.
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