Pharmacokinetics of tildipirosin in estuarine (Crocodylus porosus) and freshwater (Crocodylus siamensis) crocodiles.

Tildipirosin is a macrolide antimicrobial. It is authorised for the treatment and prevention of respiratory disease in cattle and pigs. There are no data on its administration in crocodiles. Therefore, this study evaluated the disposition kinetics of tildipirosin after intravenous (dose: 2mg/kg) and intramuscular (doses: 2 and 4mg/kg) administration in two crocodilian species (estuarine and freshwater; (n = 5). Tildipirosin plasma concentrations were quantified by a validated HPLC method. Plasma concentrations obtained at each extraction time were analysed by non-compartmental methods. In the estuarine and freshwater crocodiles, the apparent volumes of distribution of tildipirosin after intravenous administration were 0.36 ± 0.10 and 1.48 ± 0.26L/kg, respectively. These values, suggesting poorer tissue distribution, were much lower than those obtained in mammals. There was complete bioavailability of tildipirosin after intramuscular route at a dose of 2mg/kg; however, at a dose of 4mg/kg the bioavailability decreased by about 20-25%. Furthermore, the pharmacokinetics of tildipirosin were markedly different in the two crocodilian species. Considering a MIC of 0.5µg/mL, the surrogate marker AUC0→24/MIC indicates that TD would greatly exceed the value of 65h for both crocodile species and dose levels tested. This suggests that both doses (2 and 4mg/kg) may provide a bactericidal effect. Therefore, based on the absence of adverse reactions following the administration of tildipirosin in both crocodilian species, and considering its favourable pharmacokinetic properties, tildipirosin may be useful in treating infections in these reptiles.

Pharmacokinetics of marbofloxacin in freshwater crocodiles (Crocodylus siamensis) after intravenous and intramuscular administration.

To evaluate the fate and disposition of marbofloxacin (MBF) in freshwater crocodiles (Crocodylus siamensis), MBF was administered either intravenously (i.v.) or intramuscularly (i.m.) at a dosage of 2.0 mg/kg body weight. The concentrations of MBF in plasma were measured using high-performance liquid chromatography equipped with a fluorescence detector. The concentrations of MBF in the plasma were measurable up to 144 h after i.v. and i.m. administration. After the first 45 min, the mean pharmacokinetic profiles produced by the two administration routes were almost identical. No statistically significant differences in the pharmacokinetic parameters between the groups were observed. The half-life was long (about 2.5 days), the volume of distribution was large (about 1.44 L/kg), λz was small (0.01 h-1 ), and the clearance was slow (22.6 mL/h/kg). The absolute i.m. bioavailability (F%) was 105.36%. The dose of MBF administered in this study seems to produce appropriate PK-PD parameters that predict antibacterial success for disease caused by susceptible bacteria. More studies are warranted to evaluate the likely residues after administration of multiple doses.

Pharmacokinetics of amoxicillin trihydrate in Thai swamp buffaloes (Bubalus bubalis): a pilot study.

This study aimed to investigate the pharmacokinetic characteristics of amoxicillin (AMX) in Thai swamp buffaloes, Bubalus bubalis, following single intramuscular administration at two dosages of 10 and 20 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 48 h. The plasma concentrations of AMX were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of AMX in the plasma were determined up to 24 h after i.m. administration at both dosages. The Cmax values of AMX were 3.39 ± 0.18 µg/mL and 6.16 ± 0.18 µg/mL at doses of 10 and 20 mg/kg, respectively. The AUClast values increased in a dose-dependent fashion. The half-life values were 5.56 ± 0.40 h and 4.37 ± 0.23 h at doses of 10 and 20 mg/kg b.w, respectively. Based on the pharmacokinetic data and PK-PD index (T > MIC), i.m. administration of AMX at a dose of 20 mg/kg b.w might be appropriate for the treatment of susceptible Mannheimia haemolytica infection in Thai swamp buffaloes.

Disposition of a long-acting oxytetracycline formulation in Thai swamp buffaloes (Bubalus bubalis).

The present study aimed to characterize the pharmacokinetic profile of oxytetracycline long-acting formulation (OTC-LA) in Thai swamp buffaloes, Bubalus bubalis, following single intramuscular administration at two dosages of 20 and 30 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 504 h. The plasma concentrations of OTC were measured by high-performance liquid chromatography (HPLC). The concentrations of OTC in the plasma were determined up to 264 h and 432 h after i.m. administration at doses of 20 and 30 mg/kg b.w., respectively. The Cmax values of OTC were 12.11 ± 1.87 µg/mL and 12.27 ± 1.92 µg/mL at doses of 20 and 30 mg/kg, respectively. The AUClast values increased in a dose-dependent fashion. The half-life values were 52.00 ± 14.26 h and 66.80 ± 10.91 h at doses of 20 and 30 mg/kg b.w, respectively. Based on the pharmacokinetic data and PK-PD index (T > MIC), i.m. administration of OTC at a dose of 30 mg/kg b.w once per week might be appropriate for the treatment of susceptible bacterial infection in Thai swamp buffaloes.

Sulfadimethoxine in giant freshwater prawns (Macrobrachium rosenbergii): an attempt to estimate the withdrawal time by a population pharmacokinetic approach.

The fates of sulfadimethoxine (SDM) for different routes of administration were investigated in muscle tissue of giant freshwater prawns, Macrobrachium rosenbergii, following either intramuscular (i.m.) or gavage administration at a dosage of 50 mg/kg body weight (b.w.). The depletion patterns of SDM were also examined after medicated feed treatment at the feeding concentration of 10 g/kg of feed twice a day at a rate of 1% of total b.w. for five consecutive days. The concentration of SDM in prawn muscle tissue was measured using a high-performance liquid chromatography (HPLC) equipped with ultraviolet detector. Noncompartmental analyses were used to estimate basic pharmacokinetic parameters for the i.m. and gavage data, while a population model was developed to analyze the entire data set including the feed group. Using the Monte Carlo simulations, the withdrawal times (WT) for the orally administered SDM in feed supplement were determined. Maximum concentration of SDM was significantly higher in the i.m. than in the gavage group, and the area under the curve (AUC) value for relative bioavailability following gavage administration was 25.6%. Using Monte Carlo simulation, for a maximum residue limit (MRL) of 0.1 µg/g, the WT for muscle after oral administration of SDM in feed was estimated to be 67 h, while for a MRL of 0.2 µg/g, the WT was estimated to be of 54 h.

Dispositions and tissue depletion of melamine in ducks.

To evaluate the toxicokinetics and persistence of residues of melamine (MEL) in ducks, MEL was administered intravenously (i.v.) or orally (p.o.) to ducks at a dosage of 5.5 mg/kg body weight. The concentration of MEL in the plasma and various tissues was detected using HPLC equipped with an ultraviolet detector. The plasma concentration of MEL in ducks was determined up to 12 h after both i.v. and p.o. administrations. The average value of elimination half-life (t1/2ß) of MEL was 2.16 ± 0.37 and 2.01 ± 0.56 h after i.v. and p.o. administration, respectively. The absolute p.o. bioavailability was 90.79%. MEL was measurable in the liver and kidney after p.o. administration with maximum levels of 15.80 ± 1.81 and 15.49 ± 2.12 µg/g at 6 h, respectively. The results suggest that most of the administered MEL is efficiently absorbed from the gastro intestinal tract, and it has the ability to distribute into various tissues of the duck.

Pharmacokinetics of amoxicillin trihydrate in male Asian elephants (Elephas maximus) following intramuscular administration.

The purpose of this study was to investigate the pharmacokinetic characteristics of amoxicillin (AMX) trihydrate in male Asian elephants, Elephas maximus, following intramuscular administration at two dosages of 5.5 and 11 mg/kg body weight (b.w.). Blood samples were collected from 0.5 up to 72 h. The concentration of AMX in elephant plasma was measured using liquid chromatography electrospray ionization mass spectrometry. AMX was measurable up to 24 h after administration at two dosages. Peak plasma concentration (Cmax ) was 1.20 ± 0.39 µg/mL after i.m. administration at a dosage of 5.5 mg/kg b.w., whereas it was 3.40 ± 0.63 µg/mL at a dosage of 11 mg/kg b.w. A noncompartment model was developed to describe the disposition of AMX in Asian elephants. Based on the preliminary findings found in this research, the dosage of 5.5 and 11 mg/kg b.w. produced drug plasma concentrations higher than 0.25 mg/mL for 24 h after i.m. administration. Thereafter, i.m. administration with AMX at a dosage of 5.5 mg/kg b.w. appeared a more suitable dose than 11 mg/kg b.w. However, more studies are needed to determine AMX clinical effectiveness in elephants.

Toxicokinetics and absolute oral bioavailability of melamine in broiler chickens.

The objective of this study was to investigate the toxicokinetic characteristics of melamine in broilers due to the limited information available for livestock. Melamine was then administered to broiler chickens at an intravenous (i.v.) or oral (p.o.) dosage of 5.5 mg/kg of body weight, and plasma samples were collected up to 48 h. The concentration of melamine in each plasma sample was analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Melamine was measurable up to 24 h after i.v. and p.o. administration. A one-compartment model was developed to describe the toxicokinetics of melamine in broilers. Following i.v. administration, the values for the elimination half-life (t(1/2ß)), the volume of distribution (Vd ), and the clearance (CL) were 4.42 ± 1.02 h, 00.52 ± 0.18 L/kg, and 0.08 ± 0.01 L/h/kg, respectively. The absolute oral bioavailability (F) was 95.63 ± 3.54%. The results suggest that most of the administered melamine is favorably absorbed from the alimentary tract and rapidly cleared by the kidneys in broiler chickens.

Muscle tissue kinetics of oxytetracycline following intramuscular and oral administration at two dosages to giant freshwater shrimp (Macrobrachium rosenbergii).

The giant river shrimp (Macrobrachium rosenbergii), a native species of Thailand, is either exported for commercial purposes or supplied to meet the local requirements in Thailand. Limited pharmacokinetic information of the major antibiotic, oxytetracycline (OTC), is available for this freshwater shrimp. The purpose of the present study was to investigate the muscle tissue kinetics of OTC in M. rosenbergii following either intramuscular (i.m.) or oral (p.o.) administration at two dosages of 11 and 22 mg/kg body weight (b.w.). The concentration of OTC in shrimp tissues was measured using high-performance liquid chromatography (HPLC) equipped with a fluorescence detector. Muscle tissue concentrations were below the detection limit (LOD, 0.1 microg/g) after 96 and 120 h, following i.m. and p.o. administration, respectively. Peak muscle concentrations (C(max)) were 3.47 and 1.73 microg/g after i.m. and p.o. administration at a single dose of 11 mg/kg b.w. whereas they were 6.03 and 2.51 microg/g at a single dose of 22 mg/kg b.w., respectively. A noncompartment model was developed to describe the pharmacokinetics of OTC in the giant freshwater shrimp. The terminal half-lives of OTC were 28.68 and 28.09 h after i.m. and p.o. administration at a single dose of 11 mg/kg b.w., but 29.95 and 27.03 h at a single dose of 22 mg/kg b.w., respectively. The relative bioavailability was 82.32 and 64.67% following i.m. and p.o. administration, respectively. Based on the pharmacokinetic data, i.m. and p.o. administration with OTC at a dose of 11 mg/kg b.w. would be appropriate for use in giant freshwater shrimp farming. To avoid the OTC residue in shrimp muscle, it should take at least seven half-lives (8 days) to wash out the drug from the muscle of M. rosenbergii.

Fate of fusarenon-X in broilers and ducks.

In order to investigate the comparative fates and dispositions of fusarenon-X (FX) in broilers and ducks, FX was administered i.v. or orally (p.o.) to broilers and ducks. The FX and its metabolite (nivalenol, NIV) were determined in plasma and excreta using gas chromatography-mass spectrometry. The plasma concentrations of FX were determined up to 180 and 120 min in broilers and ducks, respectively, after i.v. and p.o. administration. The NIV was eliminated more slowly than its parent compound. The FX disposition fit an open 2-compartment pharmacokinetic model in broilers and ducks. The elimination half-life (t(1/2beta)) of FX was longer in ducks than in broilers. The elimination rate constant (kel) was higher in broilers than in ducks, whereas the oral bioavailability of FX was higher in ducks than in broilers. The gas chromatography-mass spectrometry profile in plasma showed that a large proportion of FX was recovered as NIV after administration of FX in both broilers and ducks. In vitro incubation of liver microsomal and cytosolic fractions with FX demonstrated that the liver and kidney are capable of the FX-to-NIV conversion. Thus, this study demonstrated that FX is absorbed more efficiently in ducks than in broilers, whereas it is eliminated more slowly in ducks than in broiler chickens. Consequently, the toxicity would have more serious consequences in ducks rather than broilers.