Pharmacokinetics and tissue residues of albendazole sulphoxide and its metabolites in donkey after intramuscular injection.

BACKGROUND: Various anti-parasitic drugs are used to control donkey parasitic diseases. The abuse of donkey drugs leads to the disposition of residues in the edible parts of treated donkeys. OBJECTIVES: The aim of this study was to (1) analyse the pharmacokinetics of ABZSO to serve as reference for the dosage regimen in donkey; and (2) calculate the withdrawal times of the ABZSO in the tissue of the donkey. METHODS: The concentrations of ABZSO and its metabolites in plasma and tissues were determined using high-performance liquid chromatography with an ultraviolet detector. Pharmacokinetic analysis was performed by the programme 3p97. RESULTS: The plasma concentrations of ABZSO and ABZSO2 concentration-time data in donkey conformed to the absorption one-compartment open model. The t 1 / 2 k e ${{{t1}} \!\mathord{/ {\vphantom { {2{{k}_{\mathrm{e}}}}}}}}$ of ABZSO was 0.67 h, whereas the t1/2 k e was 12.93 h; the Cmax and the Tp were calculated as 0.58 µg mL-1 and 3.01 h. The Vd/F of ABZSO was estimated to be 10.92 L kg-1; the area under the curve (AUC) was 12.81 µg mL-1 h. The Cmax and AUC values of ABZSO were higher than those of ABZSO2; however, t1/2 K e and Vd/F were lower. Other pharmacokinetics parameters were similar between the two metabolites. CONCLUSIONS: The results revealed that ABZSO2 was the main metabolite of ABZSO in donkey plasma. The concentrations of ABZSO and its chief metabolite (ABZSO2) were detected in liver, kidney, skin and muscle; however, ABZ-SO2NH2 was only detected in liver and kidney. The results also revealed that the depletion of ABZSO and its metabolite in donkey was longer, especially in skin.

Pharmacokinetics and ex vivo pharmacodynamics of Minocycline against Salmonella abortus equi in donkey plasma and tissue cage fluid.

Tissue Cage (TC) model was used to evaluate the pharmacokinetics and ex vivo pharmacodynamics of Minocycline (MINO) after intramuscular (IM) administration to donkeys at 4 mg/kg body-weight. The Cmax of MINO with 1.79 and 2.63 µg mL-1 was obtained at 2.96 and 1.41 h in TCF (tissue cage fluid) and plasma respectively. The absorption half-lives (t1/2ka) of MINO were calculated to be 0.71 h in TCF and 0.32 h in plasma, whereas the elimination half-lives (t1/2ke) were 10.46 h in TCF and 5.95 h in plasma. The distribution volume (Vd/F) of MINO was estimated to be 1.84 L kg-1 in TCF and 1.28 L kg-1 in plasma. The total clearance (CLb/F) of MINO was computed as 0.12 and 0.15 L/ (h·kg) in TCF and plasma respectively. The area under the concentration-time curve (AUC) of MINO was 32.77 µg mL-1h in TCF and 25.27 µg mL-1h in plasma, respectively.The ex vivo time-kill curves were established for plasma and TCF samples using Salmonella abortus equi. The MIC and MBC of MINO against salmonella were 0.08 and 0.16 µg mL-1 for plasma, 0.04 and 0.08 µg mL-1 for TCF. The plasma Cmax/MIC and AUC/MIC values after IM administration were 32.88 ± 9.87 and 315.88 ± 42.65 h, respectively. The TCF Cmax/MIC and AUC/MIC values after IM administration were 44.75 ± 9.32 and 819.25 ± 65.23 h, respectively. The values of T > MIC were approximately >36 h in plasma and > 65 h in TCF. These findings from this study suggest that MINO may be therapeutically effective in diseases of donkeys caused by salmonella when used at a dose of 4 mg/kg IM administration.

Reaction temperature alters chorzoxazone metabolism in carp (Cyprinus carpio) hepatic microsomes.

The study aimed to study the influence of different reaction temperatures on the carp (Cyprinus carpio) hepatic CYPs activity. Six groups of carp hepatic microsomes were incubated with probe drug (chorzoxazone) at 5, 10, 15, 20, 25 and 30°C separately. According to the principle of enzyme kinetics theory, the Michaelis constant (K (m)) value and maximum reaction velocity (V (max)) of CYPs (with CZX as probe) were obtained. The CYPs activity at different reaction temperatures was compared. In results, the K (m) values were separately 44.62, 31.35, 26.59, 21.75, 16.39, 29.69 µM, and the V (max) were separately 0.231, 0.234, 0.265, 0.294, 0.315, 0.239 nmol min(-1)mg(-1) at 5, 10, 15, 20, 25, 30°C. Results indicated that the enzyme CYPs activity was much higher at 25°C. It was also demonstrated that reaction temperature could affect the CYPs activity significantly. Therefore, this experiment builded a theoretical basis for the variations of fish pharmacokinetic parameters at different water temperatures and contributed to further research on the influence of water temperature on fish drug metabolism.

Pharmacokinetics and tissue residues of hydrochloric acid albendazole sulfoxide and its metabolites in crucian carp (Carassius auratus) after oral administration.

The pharmacokinetics and residues elimination of hydrochloric acid albendazole sulfoxide (ABZSO) and its metabolites were studied in healthy crucian carp (Carassius auratus, 250 ± 30 g) kept at water temperatures of 10 °C and 25 °C. The concentrations of ABZSO and its metabolites concentration in plasma and tissues were determined using high-performance liquid chromatography (HPLC) using an ultraviolet detector. The results revealed that the plasma concentration of ABZSO in plasma was significantly higher than that of albendazole sulfone (ABZSO(2)), whereas albendazole-2-aminosulfone (ABZ-SO(2)NH(2)) was not detected. The plasma concentrations of ABZSO and its main metabolite ABZSO(2) concentration-time data were fitted using a single-compartment model at 10 °C and 25 °C. The absorption half-life (t1/2ka) of ABZSO was 3.86 h at 10 °C and 1.29 h at 25 °C, whereas the elimination half-life (t1/2ke) was 16.34 h at 10 °C and 6.72 h at 25 °C; the maximum plasma concentration (C(max)) and the time-point of maximum plasma concentration (T(p)) were calculated as 3.20 µg mL(-1) and 10.58 h at 10 °C, 4.39 µg mL(-1) and 3.80 h at 25 °C. The distribution volume (V(d)/F) of ABZSO was estimated to be 1.99 L kg(-1) at 10 °C and 1.53 L kg(-1) at 25 °C; the total body clearance (CL(b)) of ABZSO were computed as 0.08 and 0.19 L/(h kg) at 10 and 25 °C, respectively; the areas under the concentration-time curve (AUC) was 118.22 µg mL(-1)h at 10 °C and 63.12 µg mL(-1)h at 25 °C. The [Formula: see text] of ABZSO(2) was found to be 6.39 °C at 10 °C and 3.73 h at 25 °C, whereas the [Formula: see text] was 12.86 h at 10 °C and 6.56 h at 25 °C; the C(max) and T(p) of ABZSO(2) was calculated as 0.78 µg mL(-1) and 12.82 h at 10 °C, 1.03 µg mL(-1) and 7.04 h at 25 °C, respectively; the V(d)/F of ABZSO(2) were estimated to be 6.43 L kg(-1) at 10 °C and 4.61 Lkg(-1) at 25 °C; the CL(b) of ABZSO(2) were computed as 0.34 and 0.49 L/(h kg) at 10 °C and 25 °C, respectively; the AUC of ABZSO(2) were 28.86 µg mL(-1)h at 10 °C and 20.52 µg mL(-1)h at 25 °C. It was demonstrated that ABZSO(2) was the main metabolite of ABZSO. The concentrations of ABZSO and its main metabolite (ABZSO(2)) were detected in muscle, skin, liver and kidney, whereas ABZ-SO(2)NH(2) was only detected in liver and kidney. The ABZSO and it metabolite (ABZSO(2)) could still be detected at 4 d time-point after administration at both temperatures in all tissues. The results revealed that the depletion of ABZSO and its metabolite (ABZSO(2)) in crucian carp was slower with a long half-life time, especially at lower water temperature.