Pharmacokinetics, tissue residues, and ex vivo pharmacodynamics of tylosin against Mycoplasma anatis in ducks

Abstract

The pharmacokinetics of tylosin were investigated in 3 groups of ducks (n = 6). They received a single dose of tylosin (50 mg/kg) by intravenous (IV), intramuscular (IM), and oral administrations, respectively. Plasma samples were collected at various time points to 24 hr post‐administration to evaluate tylosin concentration over time. Additionally, tylosin residues in tissues and its withdrawal time were assessed using 30 ducks which received tylosin orally (50 mg/kg) once daily for 5 consecutive days. After IV administration, the volume of distribution, elimination half‐life, area under the plasma concentration–time curve, and the total body clearance were 7.07 ± 1.98 L/kg, 2.04 hr, 19.47 µg hr/ml, and 2.82 L hr−1 kg−1, respectively. After IM and oral administrations, the maximum plasma concentrations were 3.70 and 2.75 µg/ml achieved at 1 and 2 hr, and the bioavailability was 93.95% and 75.77%, respectively. The calculated withdrawal periods of tylosin were 13, 8, and 5 days for kidney, liver, and muscle, respectively. For the pharmacodynamic profile, the minimum inhibitory concentration for tylosin against M. anatis strain 1,340 was 1 µg/ml. The calculated optimal oral dose of tylosin against M. anatis in ducks based on the ex vivo pharmacokinetic/pharmacodynamic modeling was 61 mg kg−1 day−1.

Pharmacokinetic-Pharmacodynamic Profile, Bioavailability, and Withdrawal Time of Tylosin Tartrate Following a Single Intramuscular Administration in Olive Flounder (Paralichthys olivaceus)

“…After IM injection at 10 mg/kg, TT reached a C max of 10.76 µg/mL at 0.25 h (T max ), after being rapidly absorbed into the serum. Although the information about pharmacokinetics of TT after IM injection in other fish may not be applicable to this study, the rapid rate of absorption was similar to the values reported (T max within 1 h) in ducks, cattle, buffaloes, and sheep [ 14 , 17 , 32 ]. The dose-normalized exposure (AUC) in olive flounder (123.55 µg/mL*h at 10 mg/kg) was 32-fold greater than the one found in the previous study (duck) that used intramuscular administration of the TT (19.14 µg/mL*h after 50 mg/kg) [ 14 ], which prolonged the duration of action as evidenced by the large exposure (AUC).…”

“…Although the information about pharmacokinetics of TT after IM injection in other fish may not be applicable to this study, the rapid rate of absorption was similar to the values reported (T max within 1 h) in ducks, cattle, buffaloes, and sheep [ 14 , 17 , 32 ]. The dose-normalized exposure (AUC) in olive flounder (123.55 µg/mL*h at 10 mg/kg) was 32-fold greater than the one found in the previous study (duck) that used intramuscular administration of the TT (19.14 µg/mL*h after 50 mg/kg) [ 14 ], which prolonged the duration of action as evidenced by the large exposure (AUC). The F of TT was calculated to be 87.35% in P. olivaceus after IM injection at 10 mg/kg, supporting the rapid and nearly complete absorption following IM administration.…”

“…The t 1/2 λ z after IV injection was 21.07 h, indicating that the rate of drug elimination is relatively slow in P. olivaceus , possibly due to differences between species. Fish have a lower metabolic rate than mammals (t 1/2 = 4.52 h) [ 16 ] and birds (t 1/2 = 2.04 h) [ 14 ], which explains the low elimination rate of TT in P. olivaceus . V z represents the volume of distribution to body tissues and fluids, and this was high in P. olivaceus (2.15 L/kg).…”

“…The high V z of TT observed in the present study suggests a high volume of distribution to body tissues of P. olivaceus , supported by the results of a previous study in which V z higher than 1 L/kg defined the high volume of distribution of the drug [ 31 ]. The extensive distribution of TT throughout the body can be attributed to high lipid solubility and moderate plasma protein binding [ 14 ]. Overall, the data suggest that TT has a long half-life and is widely distributed in P. olivaceus .…”

“…TT distributes extensively in body fluids and tissues because of its high lipid solubility and 40% plasma protein binding [ 10 , 11 ]. The pharmacokinetic profile of TT has been evaluated in various livestock, such as pigs, cattle, chickens, ducks, sheep, and goats [ 12 , 13 , 14 , 15 , 16 , 17 , 18 ]. However, there is a lack of information on the pharmacokinetics, bioavailability, and tissue depletion of TT in fish, including P. olivaceus .…”