Pharmacokinetics of lincomycin following single intravenous administration in buffalo calves

Lincomycin 10 mg kg^?1, IV in buffalo calves followed two-compartment open model with high distribution rate constant α (11.2?±?0.42 h^?1) and K ₁₂/K ₂₁ ratio (4.40?±?0.10). Distribution half-life was 0.06?±?0.01 h and AUC was 41.6?±?1.73 μg mL^?1 h. Large Vd_area (1.15?±?0.03 L kg^?1) indicated good distribution of lincomycin in various body fluids and tissues. Peak plasma level of lincomycin (71.8?±?1.83 μg mL^?1) was observed at 1 min as expected by IV route. The elimination half-life and MRT of lincomycin were short (3.30?±?0.08 and 4.32?±?0.11 h, respectively). Lincomycin 10 mg kg^?1 IV at 12-h interval would be sufficient to maintain T?>?MIC above 60 % for bacteria with minimum inhibitory concentrations (MIC) values ≤1.6 μg mL^?1. Favourable pharmacokinetic profile in buffalo calves and a convenient dosing interval suggest that lincomycin may be an appropriate antibacterial in buffalo species for gram-positive and anaerobic bacterial pathogens susceptible to lincomycin.     

Pharmacokinetics of a single intramuscular injection of cefquinome in buffalo calves

The objective of this study was to investigate the pharmacokinetics of cefquinome following single intramuscular (IM) administration in six healthy male buffalo calves. Cefquinome was administered intramuscularly (2 mg/kg bodyweight) and blood samples were collected prior to drug administration and up to 24 hr after injection. No adverse effects or changes were observed after the IM injection of cefquinome. Plasma concentrations of cefquinome were determined by high‐performance liquid chromatography. The disposition of plasma cefquinome is characterized by a mono‐compartmental open model. The pharmacokinetic parameters after IM administration (mean ± SE) were C_max 6.93 ± 0.58 μg/ml, T_max 0.5 hr, t_½kα 0.16 ± 0.05 hr, t_½β 3.73 ± 0.10 hr, and AUC 28.40 ± 1.30 μg hr/ml after IM administration. A dosage regimen of 2 mg/kg bodyweight at 24‐hr interval following IM injection of cefquinome would maintain the plasma levels required to be effective against the bacterial pathogens with MIC values ≤0.39 μg/ml. The suggested dosage regimen of cefquinome has to be validated in the disease models before recommending for clinical use in buffalo calves.     

Pharmacokinetics and pharmacodynamics of butorphanol following intravenous administration to the horse

Knych, H. K., Casbeer, H. C., McKemie, D. S., Arthur, R. M. Pharmacokinetics and pharmacodynamics of butorphanol following intravenous administration to the horse. J. vet. Pharmacol. Therap.  36 , 21–30. Butorphanol is a narcotic analgesic commonly used in horses. Currently, any detectable concentration of butorphanol in biological samples collected from performance horses is considered a violation. The primary goal of the study reported here was to update the pharmacokinetics of butorphanol following intravenous administration, utilizing a highly sensitive liquid chromatography‐mass spectrometry (LC‐MS) assay that is currently employed in many drug‐testing laboratories. An additional objective was to characterize behavioral and cardiac effects following administration of butorphanol. Ten exercised adult horses received a single intravenous dose of 0.1 mg/kg butorphanol. Blood and urine samples were collected at time 0 and at various times for up to 120 h and analyzed using LC‐MS. Mean ± SD systemic clearance, steady‐state volume of distribution, and terminal elimination half‐life were 11.5 ± 2.5 mL/min/kg, 1.4 ± 0.3 L/kg, and 5.9 ± 1.5 h, respectively. Butorphanol plasma concentrations were below the limit of detection (LOD) (0.01 ng/mL) by 48 h post administration. Urine butorphanol concentrations were below the LOD (0.05 ng/mL) of the assay in seven of 10 horses by 120 h post drug administration. Following administration, horses appeared excited as noted by an increase in heart rate and locomotion. Gastrointestinal sounds were markedly decreased for up to 24 h.     

Pharmacokinetics,urinary excretion and plasma protein binding of danofloxacin following intravenous administration in buffalo calves (Bubalus bubalis)

Pharmacokinetics, urinary excretion and plasma protein binding of danofloxacin was investigated in buffalo calves following intravenous administration at the dose rate of 1.25 mg/kg to select the optimal dosage regimen of danofloxacin. Drug concentrations in plasma and urine were measured by microbiological assaying. In vitro plasma protein binding was determined employing the equilibrium dialysis technique. The distribution and elimination of danofloxacin were rapid, as indicated by values (mean ±SD) of distribution half-life (t_1/2α = 0.16 ± 0.07 h) and elimination half-life (t_1/2β = 4.24 ± 1.78 h), respectively. Volume of distribution at steady state (Vss) = 3.98 ± 1.69 L/kg indicated large distribution of drug. The area under plasma drug concentration versus time curve (AUC) was 1.79 ± 0.28 μg/mlxh and MRT was 8.64 ± 0.61 h. Urinary excretion of danofloxacin was 23% within 48 h of its administration. Mean plasma protein binding was 36% at concentrations ranging from 0.0125 μg/ml to 1 μg/ml. On the basis of pharmacokinetic parameters obtained, it is concluded that the revision of danofloxacin dosage regimen in buffalo calves is needed because the current dosage schedule (1.25 mg/kg) is likely to promote resistance.     

Pharmacokinetics and pharmacodynamics of danofloxacin in serum and tissue fluids of goats following intravenous and intramuscular administration

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of danofloxacin in goats and the concentrations required to induce bacteriostasis, bactericidal activity, and bacterial elimination. ANIMALS: 6 healthy British Saanen goats. PROCEDURE: Danofloxacin (1.25 mg/kg of body weight) was administered i.v. and i.m. in a cross-over design with 14 days between treatments. A tissue cage was used for evaluation of drug distribution into transudate and exudate. The ex vivo antibacterial activity of danofloxacin in serum, exudate, and transudate against a caprine isolate of Mannheimia haemolytica was determined. Pharmacokinetic and pharmacodynamic data were integrated to determine the ratio of the area under the concentration versus time curve to the minimum inhibitory concentration of danofloxacin (AUIC). RESULTS: Elimination half-lives of danofloxacin in serum were 4.67 and 4.41 hours after i.v. and i.m. administration, respectively. Volume of distribution was high after administration via either route, and bioavailability was 100% after i.m. administration. Rate of penetration into exudate and transudate was slow, but elimination half-lives from both fluids were approximately twice that from serum. Drug concentrations in serum, exudate, and transudate for 9 to 12 hours after administration induced marked ex vivo antibacterial activity. For serum, AUIC24h values required for bacteriostasis, bactericidal effect, and bacterial elimination were 22.6, 29.6, and 52.4, respectively. Similar values were obtained for exudate and transudate. CONCLUSIONS AND CLINICAL RELEVANCE: Integration of danofloxacin pharmacokinetic and pharmacodynamic data obtained in goats may provide a new approach on which to base recommendations for therapeutic dosages.     

Disposition kinetics,urinary excretion and dosage regimen of kanamycin in buffalo calves following single intravenous administration

The disposition kinetics and appropriate dosage regimen for kanamycin were investigated in buffalo calves following a single intravenous dose of 10 mg/kg body weight. The distribution and elimination half-lives were 0.12±0.01 h and 1.94±0.11 h, respectively. The apparent volume of distribution and total body clearance were 0.2±0.01 L/kg and 92.9±3.69 ml/kg/h, respectively. About 74% of the administered dose was excreted in urine in 24 h. A suitable dosage regimen for the intravenous administration of kanamycin was also calculated.Abbreviation SEM standard error of the mean     

Pharmacokinetics and bioavailability of cefquinome and ceftriaxone in premature calves

The aim of this study was to evaluate the pharmacokinetics and bioavailability of cefquinome (CFQ) and ceftriaxone (CTX) following intravenous (IV) and intramuscular (IM) administrations in premature calves. Using a parallel design, 24 premature calves were randomly divided into the two antibiotic groups. Each of the six animals in the first group received CFQ (2 mg/kg) through IV or IM administration. The second group received CTX (20 mg/kg) via the same administration route. Plasma concentrations of the drugs were analyzed by high‐performance liquid chromatography and noncompartmental methods. Mean pharmacokinetic parameters of CFQ and CTX following IV administration were as follows: elimination half‐life (t_1/2λz) 1.85 and 3.31 hr, area under the plasma concentration–time curve (AUC_0–∞) 15.74 and 174 hr * μg/ml, volume of distribution at steady‐state 0.37 and 0.45 L/kg, and total body clearance 0.13 and 0.12 L hr^?1 kg^?1, respectively. Mean pharmacokinetic parameters of CFQ and CTX after IM injection were as follows: peak concentration 4.56 and 25.04 μg/ml, time to reach peak concentration 1 and 1.5 hr, t_1/2λz 4.74 and 3.62 hr, and AUC_0–∞ 22.75 and 147 hr * μg/ml, respectively. The bioavailability of CFQ and CTX after IM injection was 141% and 79%, respectively. IM administration of CFQ (2 mg/kg) and CTX (20 mg/kg) can be recommended at 12‐hr interval for treating infections caused by susceptible bacteria, with minimum inhibitory concentration values of ≤0.5 and ≤4 μg/ml, respectively, in premature calves. However, further research is indicated to assess the pharmacokinetic parameters following multiple doses of the drug in premature calves.     

Pharmacokinetics and pharmacodynamics of tramadol in horses following oral administration

Tramadol is a synthetic opioid used in human medicine, and to a lesser extent in veterinary medicine, for the treatment of both acute and chronic pain. In humans, the analgesic effects are owing to the actions of both the parent compound and an active metabolite (M1). The goal of the current study was to extend current knowledge of the pharmacokinetics of tramadol and M1 following oral administration of three doses of tramadol to horses. A total of nine healthy adult horses received a single oral administration of 3, 6, and 9 mg/kg of tramadol via nasogastric tube. Blood samples were collected at time 0 and at various times up to 96 h after drug administration. Urine samples were collected until 120 h after administration. Plasma and urine samples were analyzed using liquid chromatography–mass spectrometry, and the resulting data analyzed using noncompartmental analysis. For the 3, 6, and 9 mg/kg dose groups, C_max, T_max, and the t_1/2λ were 43.1, 90.7, and 218 ng/mL, 0.750, 2.0, and 1.5 h and 2.14, 2.25, and 2.39 h, respectively. While tramadol and M1 plasma concentrations within the analgesic range for humans were attained in the 3 and 6 mg/kg dose group, these concentrations were at the lower end of the analgesic range and were only transiently maintained. Furthermore, until effective analgesic plasma concentrations have been established in horses, tramadol should be cautiously recommended for control of pain in horses. No significant undesirable behavioral or physiologic effects were noted at any of the doses administered.     

Pharmacokinetics and pharmacodynamics of hydromorphone after intravenous and intramuscular administration in horses

ObjectiveTo compare the pharmacokinetics and pharmacodynamics of hydromorphone in horses after intravenous (IV) and intramuscular (IM) administration.Study designRandomized, masked, crossover design.AnimalsA total of six adult horses weighing [mean ± standard deviation (SD))] 447 ± 61 kg.MethodsHorses were administered three treatments with a 7 day washout. Treatments were hydromorphone 0.04 mg kg^⁻1 IV with saline administered IM (H-IV), hydromorphone 0.04 mg kg^⁻1 IM with saline IV (H-IM), or saline IV and IM (P). Blood was collected for hydromorphone plasma concentration at multiple time points for 24 hours after treatments. Pharmacodynamic data were collected for 24 hours after treatments. Variables included thermal nociceptive threshold, heart rate (HR), respiratory frequency (f_R), rectal temperature, and fecal weight. Data were analyzed using mixed-effects linear models. A p value of less than 0.05 was considered statistically significant.ResultsThe mean ± SD hydromorphone terminal half-life (t_1/2), clearance and volume of distribution of H-IV were 19 ± 8 minutes, 79 ± 12.9 mL minute^⁻1 kg^⁻1 and 1125 ± 309 mL kg^⁻1. The t_1/2 was 26.7 ± 9.25 minutes for H-IM. Area under the curve was 518 ± 87.5 and 1128 ± 810 minute ng mL^⁻1 for H-IV and H-IM, respectively. The IM bioavailability was 217%. The overall thermal thresholds for both H-IV and H-IM were significantly greater than P (p < 0.0001 for both) and baseline (p = 0.006). There was no difference in thermal threshold between H-IV and H-IM. No difference was found in physical examination variables among groups or in comparison to baseline. Fecal weight was significantly less than P for H-IV and H-IM (p = 0.02).Conclusions and clinical relevanceIM hydromorphone has high bioavailability and provides a similar degree of antinociception to IV administration.IM hydromorphone in horses provides a similar degree and duration of antinociception to IV administration.     

Pharmacokinetics of firocoxib in preweaned calves after oral and intravenous administration

The objective of this study was to determine the pharmacokinetics of intravenous and oral firocoxib in 10 healthy preweaned calves. Firocoxib (0.5 mg/kg) was initially administered i.v. to calves, and following a 14‐day washout period, animals received firocoxib orally prior to cautery dehorning. Firocoxib concentrations were determined by liquid chromatography–tandem mass spectrometry. Changes in hematology and plasma chemistry were determined using automated methods. Computer software was used to estimate pharmacokinetic parameters best described with a two‐compartment model for i.v. administration and a one‐compartment model for p.o. administration. Following i.v. dosing, the geometric mean (range) T_1/2K10 and T_1/2β were 6.7 (4.6–9.7) and 37.2 (23.5–160.4) h, respectively, V_ss was 3.10 (2.10–7.22) L/kg, and CL was 121.7 (100.1–156.7) mL/h/kg. Following oral administration, geometric mean (range) C_max was 127.9 (102.5–151.3) ng/mL, T_max was 4.0 (2.6–5.6) h, and T_1/2K10 was 18.8 (14.2–25.5) h. Bioavailability of oral firocoxib was calculated using the AUC derived from both study populations to be 98.4% (83.1–117.6%). No adverse clinical effects were evident following firocoxib administration. Pharmacokinetic analysis of i.v. and p.o. firocoxib indicates high bioavailability and a prolonged terminal half‐life in preweaned calves.     

Pharmacokinetics of buprenorphine following intravenous administration in dogs

OBJECTIVE: To determine pharmacokinetics of buprenorphine in dogs after i.v. administration. ANIMALS: 6 healthy adult dogs. PROCEDURES: 6 dogs received buprenorphine at 0.015 mg/kg, i.v. Blood samples were collected at time 0 prior to drug administration and at 2, 5, 10, 15, 20, 30, 40, 60, 90, 120, 180, 240, 360, 540, 720, 1,080, and 1,440 minutes after drug administration. Serum buprenorphine concentrations were determined by use of double-antibody radioimmunoassay. Data were subjected to noncompartmental analysis with area under the time-concentration curve to infinity (AUC) and area under the first moment curve calculated to infinity by use of a log-linear trapezoidal model. Other kinetic variables included terminal rate constant (k(el)) and elimination half-life (t(1/2)), plasma clearance (Cl), volume of distribution at steady state (Vd(ss)), and mean residence time (MRT). Time to maximal concentration (T(max)) and maximal serum concentration (C(max)) were measured. RESULTS: Median (range) values for T(max) and MRT were 2 minutes (2 to 5 minutes) and 264 minutes (199 to 600 minutes), respectively. Harmonic mean and pseudo SD for t(1/2) were 270+/-130 minutes; mean +/- SD values for remaining pharmacokinetic variables were as follows: C(max), 14+/-2.6 ng/mL; AUC, 3,082+/-1,047 ng x min/mL; Vd(ss), 1.59+/-0.285 L/kg; Cl, 5.4+/-1.9 mL/min/kg; and, k(el), 0.0026+/-0.0,012. CONCLUSIONS AND CLINICAL RELEVANCE: Pharmacokinetic variables of buprenorphine reported here differed from those previously reported for dogs. Wide variations in individual t(1/2) values suggested that dosing intervals be based on assessment of pain status rather than prescribed dosing intervals.