Higher bioavailability of doxycycline in broiler chickens with a novel in-feed pharmaceutical formulation.
Bioavailability of a new, long-acting (LA) pharmaceutical preparation for administering doxycycline as in-feed medication to broiler chickens was compared to the standard in-feed administration of doxycycline. A commercial poultry house harboring Ross-308 broiler chickens, weighing 450 g, was divided into 7 sections as follows: doxy-FOLA group (n = 6,000 chickens divided into 3 replicates) medicated with 10% doxycyline, long-acting pellets at a dose of 400 g of doxycycline HCl/ton of food, resulting in a calculated dose of 48 mg/kg for 5 d; doxy-ref group (n = 6,000, divided into 3 replicates) medicated as for doxy-FOLA, but using a 20% commercial preparation of doxycycline. A third group of 300 broiler chickens (divided into 3 replicates), received a single IV dose of 48 mg/kg from a 2.4% solution of doxycycline HCl under ketamine anesthesia. Blood samples were obtained at designated times, serum was harvested, and doxycycline concentrations determined by high-performance liquid chromatography (HPLC). Bioavailability values were 156% and 227% on d 1 and 5 for doxy-FOLA and 13% and 23% for doxy-ref, on the same days. Mean residence time (MRT) and elimination half-life (T½β) were statistically different (P < 0.05) in doxy-FOLA group as compared to doxy-ref group (MRT: 26 h and 5.2 h; and T½β: 18 h vs 3 h, on the first day for doxy-FOLA and doxy-ref, respectively). Based on 3 levels of bacterial sensitivity of E. coli derived from a small survey carried out (i.e., 1.0, 2.0, and 4.0 μg/mL) and considering pharmacokinetic/pharmacodynamic (PK/PD) ratios required for this time-dependent antibacterial drug, it is possible to postulate that doxy-FOLA outstrips the reference preparation maintaining higher and more prolonged serum concentrations of doxycycline and consequently complying better with PK/PD ratios regarded as optimal for this drug. The advantages of using doxy-FOLA in poultry medicine include a more comprehensive use of the active principle, which in turn should have a better impact on bacterial diseases. Yet, a longer withdrawal time is anticipated based on an almost 4-fold increment in the MRT value.
Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia. Universidad Nacional Autónoma de México, Av. Universidad 3000, Delegación Coyoacán, Ciudad de México C.P. 04510, México.
Lilia
L
Gutiérrez
NF Feed Products Mexico S.A. de C.V. de la Industria 20, Fraccionamiento Industrial La Luz, Cuautitlán, México, C.P. 54830, México.
Juan
J
Zermeño
Departamento de Parasitología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Av. Universidad 3000, Delegación Coyoacán, Ciudad de México C.P. 04510, México.
Yazmín
Y
Alcalá
Departamento de Fisiología y Farmacología, Facultad de Medicina Veterinaria y Zootecnia. Universidad Nacional Autónoma de México, Av. Universidad 3000, Delegación Coyoacán, Ciudad de México C.P. 04510, México.
Héctor
H
Sumano
D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001682:Biological Availability; D002645:Chickens / Q000378:metabolism; D004318:Doxycycline / Q000493:pharmacokinetics*; D004339:Drug Compounding / Q000662:veterinary*; D004926:Escherichia coli / Q000502:physiology; D004927:Escherichia coli Infections / Q000517:prevention & control / Q000662:veterinary*; D005260:Female; D008297:Male; D011201:Poultry Diseases / Q000517:prevention & control*; D011897:Random Allocation
D000900:Anti-Bacterial Agents; D004318:Doxycycline
AUC/MIC; bioavailability; chicken; doxycycline; new-preparation