Metal ion-oxytetracycline pharmacokinetic interactions after oral co-administration in broiler chickens

Abstract

The influence of the composition of calcium (Ca(2+)), magnesium (Mg(2+)), and iron (Fe(3+)) ions in two concentration levels (low-500 mg/L of CaCl2, 125 mg/L of MgCl2, and 10 mg/L of FeCl3 and high-2,500 mg/L of CaCl2, 625 mg/L of MgCl2, and 50 mg/L of FeCl3) contained in water on the pharmacokinetics (PK) of oxytetracycline (OTC) was determined. OTC hydrochloride was administered at a dose of 25 mg/kg of body weight to broiler chickens divided into four groups of nine birds each, including 3 oral groups (in deionized water -control, in water with low ion concentration, and in water with high ion concentration) and 1 intravenous group. OTC concentrations in plasma were determined using liquid chromatography-tandem mass spectrometry, after which non-compartmental pharmacokinetic analysis was conducted.The absolute bioavailability of OTC in the group of birds exposed to higher ions concentration was reduced (8.68% ± 2.56) as compared to the control (13.71% ± 2.60). Additionally, in this group, decrease in PK parameters such as: area under the concentration-time curve from 0 to infinity (15.36 μg × h/mL ± 4.36), from 0 to t (14.78 μg × h/mL ± 4.37), area under the first moment of curve from 0 to t (107.54 μg × h/mL ± 36.48), and maximum plasma concentration (2.13 μg/mL ± 0.32) were also observed. It is noteworthy, all mentioned parameters demonstrated a downward trend with high correlation coefficient (P = 0.004, P = 0.002, P = 0.005, P = 0.004, P = 0.011, respectively), reflecting the influence of increasing concentrations of Ca(2+), Mg(2+), and Fe(3+) ions on the decreasing absorption rate of OTC.Based on the current research results, it can be assumed that high concentrations of several ions applied concomitantly are able to decrease the absorption of OTC from gastrointestinal tract in broiler chickens. This occurrence might impair the drug's clinical efficacy toward some pathogenic microorganisms. It implies that using OTC on a farm may require administration of higher doses than the routine one when infections are caused by less sensitive pathogens.

Impact of water hardness on oxytetracycline oral bioavailability in fed and fasted piglets

“…Similar results were obtained by Ziółkowski et al. () after administration of OTC in water containing different concentrations of divalent cations to broiler chickens. Results obtained in both studies could be related to changes in conformational structure of chelated OTC that affect its interaction with mucosal cells’ membrane decreasing absorption, hence AUC 0–24 and F %.…”

Potential interactions between an oral fosfomycin formulation and feed or drinking water: Impact on bioavailability in piglets

“…It is imperative to acquire and seriously ponder this information to support decisions on eligibility of antibiotic pharmaceutical formulations and the vehicle for their administration in order to harness the benefits of these drugs while taking responsibility on their use. The deleterious impact that water or feed components can have on antibiotic absorption and bioavailability have been previously demonstrated by other authors (Abuhelwa et al, 2017;Burow & Kasbohrer, 2016;Decundo et al, 2019;Ferran & Roques, 2019;Soraci et al, 2014;Vandael et al, 2019;Ziółkowski et al, 2016) and further confirmed in the present work. Thus, the incompatibility of a drug with its vehicle of administration would lead to erratic dosage, unpredicted therapeutic outcomes, environmental accumulation, and development of antimicrobial resistance.…”

Pharmacokinetics of tigecycline in turkeys following different routes of administration

“…In turn, after intravenous administration, TIG reached the average value of this parameter equal approximately 23 hr, which is several fold higher than the value recorded after intravenous injection of doxycycline (Anadon et al., ) or MINO (Grabowski, ), but close to the results obtained after i.v. administration of oxytetracycline in broiler chickens (Ziółkowski, Grabowski, et al., ; Ziółkowski, Jasiecka, et al., ). These findings suggest that the t 1/2β of intravenously given TIG in birds is closer in value to this parameter determined for natural TCs than for modified TCs.…”