title: Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water.
abstract: The recommended use of doxycycline (DC) to broiler chicken is 100 mg/L via the drinking water and a 7-day withdrawal time (WDT). However, study of a higher dosage is desirable because of the possible increase of antimicrobial resistance and disease spectrum. Tissue DC residues exceeding the current maximum residue levels (MRL) was our major concern. Therefore, serum concentration and tissue depletion of DC hyclate after administration of 200 mg/L of DC in the drinking water for five consecutive days were studied. The steady-state DC concentration (8.3 ± 0.9 μg/mL) was reached on the third day of medication. The elimination constant (0.05 ± 0.01 1/h), half-life (14.9 ± 1.4 h), area under concentration versus time curve (81.0 ± 9.9 h·μg/mL) and mean residence time (22.7 ± 2.5 h) were obtained using a non-compartmental pharmacokinetic model. It was determined that the current 7-day WDT regulation was still legitimate for the kidney and liver as well as for the breast and leg muscles, which were estimated by linear regression analysis of the 99% upper distribution limit. The unregulated heart and gizzard were considered safe even when the lowest MRL of muscle (100 ng/g) was applied. While at the present time the extra-label use of drugs is only allowed under specific conditions, in the future it may become necessary to increase the general dosage of DC, and the current results suggest a safe range of DC hyclate in chicken; however, skin/fat tissue residues warrant further studies.
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University , No. 250, Kuo-Kuang Rd., Taichung 402 , Taiwan.
authors.forename: Pai-Feng
authors.initials: PF
authors.lastname: Hsiao
authors.affiliation: Institute of Veterinary Medicine, School of Veterinary Medicine, National Taiwan University , Taipei , Taiwan.
authors.forename: Shao-Kuang
authors.initials: SK
authors.lastname: Chang
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University , No. 250, Kuo-Kuang Rd., Taichung 402 , Taiwan.
authors.forename: Tien-Huan
authors.initials: TH
authors.lastname: Hsu
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University , No. 250, Kuo-Kuang Rd., Taichung 402 , Taiwan.
authors.forename: Kuang-Po
authors.initials: KP
authors.lastname: Li
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung Hsing University , No. 250, Kuo-Kuang Rd., Taichung 402 , Taiwan.
authors.forename: Chi-Chung
authors.initials: CC
authors.lastname: Chou
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000008:administration & dosage / Q000493:pharmacokinetics*; D060766:Drinking Water; D004350:Drug Residues / Q000493:pharmacokinetics*; D006207:Half-Life
chemical_list: D060766:Drinking Water; D004318:Doxycycline
keywords: Doxycycline hyclate; broiler; heart and gizzard; pharmacokinetics; withdrawal time