Pharmacokinetics of famotidine in goats after intravenous administration.

There is currently limited pharmacokinetic data for the use of famotidine in goats for treatment and prevention of abomasal ulceration. The objective of this study was to determine the pharmacokinetic parameters after a single intravenous administration of famotidine (0.6 mg/kg). Famotidine was administered to six healthy goats and plasma samples were collected over a 24-h period. The famotidine concentration was measured using reverse phase high-performance liquid chromatography (HPLC). Non-compartmental analysis was then used to determine the pharmacokinetic parameters. The maximum plasma concentration was estimated at 5476.68 ± 1530.51 ng/mL and elimination half-life was estimated at 18.455 ± 13.26 min. The mean residence time was determined to be 19.85 ± 12.14 min with the apparent volume of distribution being estimated at 321.924 ± 221.667. The area under the curve was determined to be 54230.08 ± 24947.6 min*ng/mL. Total exposure and elimination half-life were less than what has been reported in cattle and horses. Future research evaluating the pharmacokinetics of subcutaneous administration and looking at the pharmacodynamics of famotidine in goats is needed to determine the effectiveness of famotidine on raising pH levels of the abomasum.

The pharmacokinetics and pharmacodynamics of esomeprazole in sheep after intravenous dosing.

Abomasal (gastric) ulceration is a morbidity in sheep, and currently, there is a paucity of pharmacokinetic and pharmacodynamic data for gastroprotectant drugs reported for this species. The proton pump inhibitor esomeprazole has been used in small animal and human patients for gastroprotection via increasing the gastric pH. The objective of this study was to report the pharmacokinetic parameters and pharmacodynamic effect of esomeprazole in sheep after single intravenous dosing. Four healthy adult Southdown cross ewes had blood collected over a 24 h time period after single intravenous dosing of esomeprazole at 1.0 mg/kg. Abomasal fluid was sampled over 24 h before and after esomeprazole administration. Plasma samples were analyzed for concentrations of esomeprazole and the esomeprazole metabolite, esomeprazole sulfone by high performance liquid chromatography. Pharmacokinetic and pharmacodynamic data were evaluated with specialized software. Esomeprazole was rapidly eliminated after IV administration. Elimination half-life, area under the curve, initial concentration (C0), and clearance were 0.2 h, 1,197 h*ng/mL, 4,321 ng/mL, and 0.83 mL/h/kg, respectively. For the sulfone metabolite elimination half-life, area under the curve and maximum concentration were 0.16 h, 22.5 h*ng/mL, and 65.0 ng/mL, respectively. Abomasal pH was significantly elevated from 1 to 6 h after administration and remained above 4.0 for at least 8 h after administration. No adverse effects were noted in these sheep. Esomeprazole was rapidly eliminated in sheep, similar to goats. Abomasal pH was increased, but future studies will be necessary to develop a clinical management approach to the use of esomeprazole in sheep.

Pharmacokinetics and Egg Residues of Oral Meloxicam in Bantam Cochin Chickens.

Backyard poultry are commonly treated in veterinary hospitals; however, there is limited information regarding appropriate dosing of medications and withdrawal times for eggs. Six healthy adult bantam Cochin hens were given a single oral dose of meloxicam (1 mg/kg). Meloxicam plasma concentrations and egg residues were analyzed by high-performance liquid chromatography. Noncompartmental analysis was used to calculate pharmacokinetic parameters. The apparent terminal half-life, maximum concentration, and time to maximum concentration were 5.94 ± 0.92 hours, 7.03 ± 2.68 µg/mL, and 2.83 ± 1.33 hours, respectively. Meloxicam was detected in egg whites for 4.8 ± 1.5 days and egg yolks for 9.8 ± 2.4 days. Results were compared with previous studies in white leghorn and Columbian Wyandotte hens. Bantam Cochin hens demonstrated a significantly longer mean apparent terminal half-life, greater area under the curve, smaller elimination rate constant, and longer egg residue times compared with white leghorn hens. However, the pharmacokinetic results from the bantam Cochin hens did not significantly differ from those reported for the Columbian Wyandotte hens. Until pharmacodynamic studies can be performed, dosing of oral meloxicam in bantam Cochins should follow recommendations for Columbian Wyandotte hens to reduce the likelihood of adverse effects. These results better inform appropriate dosing of meloxicam in domestic hens, as well as recommended withdrawal times for egg consumption.

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration.

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (V z ) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 µg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 µg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration.

The influence of storage time on ponazuril concentrations in feline plasma.

BACKGROUND: The pharmacokinetics of ponazuril have been determined in several species; however, there is very little information on the stability of the drug after storage for long periods of time. This study was undertaken to determine the stability of ponazuril in plasma samples stored at -80 °C, which is the temperature most commonly used in the author's laboratory. METHOD: Spiked plasma samples (0.3, 7.5, and 15 µg/mL) were stored at -80 °C for three months. Analysis occurred on the first day and then once a week for the following twelve weeks. The drug was extracted using a chloroform extraction and separated by high performance liquid chromatography using ultraviolet detection. RESULTS: There was no loss of drug for any concentration for the first four weeks of storage. There was an average loss of less than 5% from day 35 through day 70 and an average loss of 6% on day 77 and 84. The data suggest that ponazuril is stable for 4 weeks when stored at -80 °C and undergoes minimal loss in the remaining 8 weeks.

Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report.

Background: Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats. Objective: The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats. Methods: Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis. Results: Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 µg/mL, 0.8 h, and 0.2 hr*µg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study. Conclusion: The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.

Bioanalytical RP-HPLC method for the determination of ponazuril in plasma.

The goal of this investigation was to establish a reliable technique for the quantitation of ponazuril in limited sample volumes. Samples were extracted with chloroform and separation was achieved with a Symmetry RP18 column. Ultraviolet absorption was measured at 254 nm. A combination of 0.1% formic acid and acetonitrile (50:50) was used as the mobile phase. The calibration curve was linear from 0.1-25 µg/mL, with a lower limit of quantification of 0.1 µg/mL with a 100 µL sample. The precision and accuracy were well within the range set by the Food and Drug Administration and the recovery was over 95%. This technique was used to analyze ponazuril samples and found to be appropriate for pharmacokinetic studies.

Determination of ceftazidime in plasma by RP-HPLC and ultraviolet detection.

A simple high-performance liquid chromatography method for the determination of ceftazidime in plasma has been developed. Using an ultrafiltration technique samples were separated by reverse-phase high-performance liquid chromatography on a Symmetry C18 4.6 × 250 mm column (5.0 µm) and ultraviolet absorbance was measured at 260 nm. The mobile phase was a mixture of 10 mm potassium phosphate monobasic pH 2.5 with phosphoric acid and acetonitrile (90:10). The standard curve ranged from 0.1 to 100 µg/ml. Intra- and inter-assay variability for ceftazidime was <12%, and the average recovery was 89%. The lower limit of quantification was 0.1 µg/ml. This method has been used successfully to analyze frog plasma samples at this institution and it could be applied to other small volume samples in a clinical or research setting.