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: 2 mg/kg) and intramuscular (doses: 2 and 4 mg/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 ± 0.26 L/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 2 mg/kg; however, at a dose of 4 mg/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 0.5 µg/mL, the surrogate marker AUC0-24/MIC indicates that tildipirosin would greatly exceed the value of 65 h for both crocodile species and dose levels tested. This suggests that both doses (2 and 4 mg/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.

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.

Dispositions and residue depletion of enrofloxacin and its metabolite ciprofloxacin in muscle tissue of giant freshwater prawns (Macrobrachium rosenbergii).

Fates and residue depletion of enrofloxacin (ER) and its metabolite ciprofloxacin (CP) were examined in giant freshwater prawns, Macrobrachium rosenbergii, following either single oral (p.o.) administration of ER at a dosage of 10 mg/kg body weight (b.w.) or medicated-feed treatment at the feeding concentration of 5 g/kg of feed for five consecutive days. The concentrations of ER and CP in prawn muscle tissues were measured simultaneously using high-performance liquid chromatography (HPLC) equipped with a fluorescence detector. Muscle tissue concentrations of ER and CP were below the detection limit (LOD, 0.015 microg/g for ER; 0.025 microg/g for CP) after 360 and 42 h, following single p.o. administration respectively. Peak muscle concentration (C(max)) of ER was 1.98 +/- 0.22 microg/g whereas CP was measurable at concentrations close to the detection limit of the analytical method after p.o. administration at a single dosage of 10 mg/kg b.w. The concentration of ER in prawn muscle tissue with respect to time was analyzed with a non-compartmental pharmacokinetic model. The elimination half-life and area under the curve of ER were 39.33 +/- 7.27 h and 168.7 +/- 28.7 microg x h/g after p.o. administration at a single dose of 10 mg/kg x b.w. respectively. In medicated-feed treated group, ER was detectable in prawn muscle tissue 11 days postdosing at the dose of 5 g/kg of feed for five consecutive days, which is the value corresponding to the maximum residue limit (MRL) of ER in animal products. The maximum concentrations of ER and CP were 2.77 +/- 0.91 and 0.06 +/- 0.006 microg/g during medicated-feed treatment and postdosing respectively. The values of elimination half-life and absorption half-life of ER after single p.o. administration at a dosage of 10 mg/kg b.w. corresponded well with the values determined from medicated-feed treated group, showing 41.01 +/- 6.62 and 11.36 +/- 3.15 h respectively in M. rosenbergii. Based on data derived from this study, to avoid the ER residue in prawn muscle, it should take at least 11 days postcessation of medicated feed containing ER at the dose concentration of 5 g/kg of feed twice a day at a rate of 1% of total body weight for five consecutive days to wash out the drug from the muscle of M. rosenbergii.