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 (C_max) 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_1/2β), the volume of distribution (V_d), 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.     

Pharmacokinetics of marbofloxacin in Green sea turtles (Chelonia mydas) following intravenous and intramuscular administration at two dosage rates

Limited pharmacokinetic information to establish suitable therapeutic plans is available for green sea turtles. Therefore, the present study was conducted to evaluate the pharmacokinetic characteristics of marbofloxacin (MBF) in the green sea turtle, Chelonia mydas, following single intravenous (i.v.) or intramuscular (i.m.) administration at two dosages of 2 and 4 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. MBF in plasma was extracted using liquid–liquid extraction and analyzed by a validated high-performance liquid chromatography (HPLC). MBF was quantifiable from 15 min to 96 hr after i.v. and i.m. administrations at two dose rates. A noncompartmental model was used to fit the plasma concentration of MBF versus time curve for each green sea turtle. The t_1/2λz value, similar for both the dosages (22–28 hr), indicated that the overall rate of elimination of MBF in green sea turtles is relatively slow. The average i.m. F% ranged 88%–103%. MBF is a concentration-dependent drug and the AUC/MIC ratio is the best PK/PD predictor for its efficacy. The MBF dosage of 4 mg/kg appeared to produce an appropriate value of the PK-PD surrogate that predicts antibacterial success for disease caused by susceptible bacteria. In contrast, i.m. administration of MBF at a dosage of 2 mg/kg b.w. was not found to produce a suitable PK-PD surrogate index. However, further studies of multiple doses and plasma binding proteins are warranted to confirm an appropriate dosage regimen.     

Pharmacokinetic profiles of amoxicillin trihydrate in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at two doses

The aim of the present study was to elucidate the pharmacokinetic profiles of amoxicillin trihydrate (AMX) in Siamese freshwater crocodiles (Crocodylus siamensis). Crocodiles were administered a single intramuscular injection of AMX, at a dose of either 5 or 10 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 120 hr. The plasma concentrations of AMX were measured using a validated liquid chromatography tandem-mass spectrometry method. AMX plasma concentrations were quantifiable for up to 72 hr (5 mg/kg b.w.) and 96 hr (10 mg/kg b.w.). The elimination half-life (t_1/2λz) of AMX following dosing at 5 mg/kg b.w. (8.72 ± 0.61 hr) was almost identical to that following administration at 10 mg/kg b.w (8.98 ± 1.13 hr). The maximum concentration and area under the curve from zero to the last values of AMX increased in a dose-dependent fashion. The average binding percentage of AMX to plasma protein was 21.24%. Based on the pharmacokinetic data, susceptibility break point, and the surrogate PK-PD index (T > MIC, 0.25 μg/ml), intramuscular administration of AMX at dose of 5 mg/kg b.w. every 4 days might be appropriate for the treatment of susceptible bacterial infections in freshwater crocodiles.     

Clinical Pharmacokinetics and Effects of Vincristine Sulfate in Dogs with Transmissible Venereal Tumor (TVT)

This study was conducted to evaluate the pharmacokinetic characteristics of vincristine and their correlation with its clinical effects in dogs with transmissible venereal tumor (TVT). Dogs with TVT were intravenously administered vincristine sulfate at a dose of 0.7 mg/m² of body surface area. Blood samples were collected starting from 5 min to 48 hr after drug administration. The plasma concentration of vincristine was determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters of vincristine were characterized using a two-compartmental pharmacokinetic model. The volume of distribution, distribution half-life, elimination half-life and plasma clearance were 0.660 ± 0.210 l/kg, 21.5 ± 6.90 min, 47.6 ± 14.2 min and 0.010 ± 0.001 l/min/kg, respectively. Tumor regression was determined at weekly interval by a physical examination and histopathological analysis. In our study, three to eight administrations of vincristine at a dose of 0.7 mg/m² were able to induce a complete tumor regression without any evidence of gross lesion of disease. Therefore, this investigation provides the pharmacokinetic characteristics of vincristine in dogs with TVT, which may be used as an integration tool to gain a better understanding of the disposition properties of the drug and the correlation of these properties with the drug’s clinical effects. In addition, we validated the LC-MS/MS method and found that it is suitable for the pharmacokinetic study of vincristine in dog plasma.     

Breeding Novel Short Grain Rice for Tropical Region to Combine Important Agronomical Traits,Biotic Stress Resistance and Cooking Quality in Koshihikari Background

Breeding program strategies to develop novel short grain white rice varieties such as japonica (short grain) that introgress biotic stress resistance and high grain quality have been developed using indica rice (Pin Kaset + 4 and Riceberry) for applications in japonica rice (Koshihikari) improvement. Four breeding lines showing promising agronomic performance with short grain and low amylose content (< 20%) were obtained. In addition, sensory testing of these breeding lines showed high scores that similar to Koshihikari. Two promising lines, KP48-1-5 and KP48-1-9, which possessed a combination of four genes resistance to different biotic stresses (Bph3 + TPS + Xa21 + Pi-ta) and four genes for grain quality (GS3 + SSIIa + wx^b + badh2), were developed using marker-assisted selection (MAS) with the pedigree method. The current study clearly illustrated the successful use of MAS in combining resistance to multiple biotic stresses while maintaining a high yield potential and preferred grain quality. Moreover, the results indicated that this breeding program, which includes crossing temperate japonica with indica, can create novel short grain rice varieties adapted to a tropical environment, like the japonica type.     

Pharmacokinetics of tolfenamic acid in Hawksbill turtles (Eretmochelys imbricata) after single intravenous and intramuscular administration

To the best of our knowledge, limited pharmacokinetic information to establish suitable therapeutic plans is available for Hawksbill turtles. Therefore, the present study aimed to assess the pharmacokinetic features of tolfenamic acid (TA) in Hawksbill turtles, Eretmochelys imbricata, after single intravenous (i.v.) and intramuscular (i.m.) administration at dosage 4 mg/kg body weight (b.w.). The study (parallel design) used 10 Hawksbill turtles randomly divided into equal groups. Blood samples were collected at assigned times up to 144 hr. The concentrations of TA in plasma were quantified by a validated liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). The concentration of TA in the experimental turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The C_max values of TA were 89.33 ± 6.99 µg/ml following i.m. administration. The elimination half-life values were 38.92 ± 6.31 hr and 41.09 ± 9.32 hr after i.v. and i.m. administration, respectively. The absolute i.m. bioavailability was 94.46%, and the average binding percentage of TA to plasma protein was 31.39%. TA demonstrated a long half-life and high bioavailability following i.m. administration. Therefore, the i.m. administration is recommended for use in clinical practice because it is both easier to perform and provides similar plasma concentrations to the i.v. administration. However, further studies are needed to determine the clinical efficacy of TA for treatment of inflammatory disease after single and multiple dosages.     

Pharmacokinetics of enrofloxacin and its metabolite ciprofloxacin in freshwater crocodiles (Crocodylus siamensis) after intravenous and intramuscular administration

To the best of the authors’ knowledge, pharmacokinetic information to establish suitable therapeutic plans for freshwater crocodiles is limited. Therefore, the purpose of this study was to clarify the pharmacokinetic characteristics of enrofloxacin (ENR) in freshwater crocodiles, Crocodylus siamensis, following single intravenous and intramuscular administration at a dosage of 5 mg/kg body weight (b.w.). Blood samples were collected at assigned times up to 168 hr. The plasma concentrations of ENR and its metabolite ciprofloxacin (CIP) were measured by liquid chromatography tandem–mass spectrometry. The concentrations of ENR and CIP in the plasma were quantified up to 144 hr after both the administrations. The half-life was long (43–44 hr) and similar after both administrations. The absolute i.m. bioavailability was 82.65% and the binding percentage of ENR to plasma protein ranged from 9% to 18% with an average of 10.6%. Percentage of CIP (plasma concentrations) was 15.9% and 19.9% after i.v. and i.m. administration, respectively. Based on the pharmacokinetic data, susceptibility break point and PK-PD indexes, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be appropriate for treatment of susceptible bacteria (MIC > 1 μg/mL) in freshwater crocodiles, C. siamensis.     

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 ceftriaxone in freshwater crocodiles (Crocodylus siamensis) after intramuscular administration at two dosages

One of the major obstacles to the successful treatment of infectious disease in freshwater crocodile species is incorrect dosing of antibiotics. There are few reports on pharmacokinetics and dosage regimens of antimicrobial drugs in crocodiles. The purpose of the present study was to clarify the pharmacokinetic characteristics of ceftriaxone (CEF) in Siamese freshwater crocodiles (Crocodylus siamensis). Freshwater crocodiles, Crocodylus siamensis, in breeding farms were treated with a single intramuscular administration of CEF at two dosages, 12.5 and 25 mg/kg body weight (b.w.). Blood samples were collected at preassigned times up to 168 hr. The plasma concentrations of CEF were measured by a validated method through liquid chromatography tandem-mass spectrometry. CEF plasma concentrations were quantified up to 72 and 96 hr after low- and high-dose administration, respectively. The C_max values of CEF were 24.61 ± 5.15 µg/ml and 26.39 ± 2.81 µg/ml at dosages of 12.5 and 25 mg/kg b.w., respectively. The AUC_last values increased in a dose-dependent fashion. The half-life values were not statistically different between the groups (around 20 hr). The average binding percentage of CEF to plasma protein was 53.78 ± 2.11%. Based on the pharmacokinetic data, susceptibility break-point and the surrogate PK-PD index (T > MIC, 0.2 μg/ml), i.m. administration of CEF at a dose of 12.5 mg/kg b.w. might be appropriate for initiating treatment of susceptible bacterial infections in freshwater crocodiles.