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Ciprofloxacin pharmacokinetics and oral absorption of generic ciprofloxacin tablets in dogs Texto completo
2012
Papich, Mark G.
Objective: To determine the pharmacokinetics of ciprofloxacin in dogs, including oral absorption following administration of generic ciprofloxacin tablets. Animals: 6 healthy Beagles. Procedures: In a crossover study design, ciprofloxacin was administered as a generic tablet (250 mg, PO; mean dose, 23 mg/kg) and solution (10 mg/kg, IV) to 6 dogs. In a separate experiment, 4 of the dogs received ciprofloxacin solution (10 mg/mL) PO via stomach tube (total dose, 250 mg). Blood samples were collected before (time 0) and for 24 hours after each dose. Plasma concentrations were analyzed with high-pressure liquid chromatography. Pharmacokinetic analysis was performed by means of compartmental modeling. Results: When ciprofloxacin was administered as tablets PO, peak plasma concentration was 4.4 μg/mL (coefficient of variation [CV], 55.9%), terminal half-life (t1/2) was 2.6 hours (CV, 10.8%), area under the time-concentration curve was 22.5 μg•h/mL (CV, 62.3%), and systemic absorption was 58.4% (CV, 45.4%). For the dose administered IV, t1/2 was 3.7 hours (CV, 52.3%), clearance was 0.588 L/kg/h (CV, 33.9%), and volume of distribution was 2.39 L/kg (CV, 23.7%). After PO administration as a solution versus IV administration, plasma concentrations were more uniform and consistent among dogs, with absorption of 71% (CV, 7.3%), t1/2 of 3.1 hours (CV, 18.6%), and peak plasma concentration of 4.67 μg/mL (CV, 17.6%). Conclusions and Clinical Relevance: Inconsistent oral absorption of ciprofloxacin in some dogs may be formulation dependent and affected by tablet dissolution in the small intestine. Because of the wide range in oral absorption of tablets, the dose needed to reach the pharmacokinetic-pharmacodynamic target concentration in this study ranged from 12 to 52 mg/kg (CV, 102%), with a mean dose of 25 mg/kg, once daily, for bacteria with a minimum inhibitory concentration ≤ 0.25 μg/mL.
Mostrar más [+] Menos [-]Comparison of pharmacokinetic variables for creatinine and iohexol in dogs with various degrees of renal function Texto completo
2012
Collignon, Cecile M. | Heiene, Reidun | Queau, Yann | Reynolds, Brice S. | Craig, Amanda J. | Concordet, Didier | Harran, Nathaniel X. | Risoen, Unni | Balouka, David | Faucher, Mathieu R. | Eliassen, Knut A. | Biourge, Vincent | Lefebvre, Herve P.
Comparison of pharmacokinetic variables for creatinine and iohexol in dogs with various degrees of renal function Texto completo
2012
Collignon, Cecile M. | Heiene, Reidun | Queau, Yann | Reynolds, Brice S. | Craig, Amanda J. | Concordet, Didier | Harran, Nathaniel X. | Risoen, Unni | Balouka, David | Faucher, Mathieu R. | Eliassen, Knut A. | Biourge, Vincent | Lefebvre, Herve P.
Objective: To compare pharmacokinetics and clearances of creatinine and iohexol as estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function. Animals: 50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function. Procedures: Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA. Results: Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods. Conclusions and Clinical Relevance: Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range.
Mostrar más [+] Menos [-]Comparison of pharmacokinetic variables for creatinine and iohexol in dogs with various degrees of renal function Texto completo
2012
Collignon, Cécile M | Heiene, Reidun | Queau, Yann | Reynolds, Brice S. | Craig, Amanda J | Concordet, Didier | Harran, Nathaniel X | Risoen, Unni | Balouka, David | Faucher, Mathieu R | Eliassen, Knut A | Biourge, Vincent | Lefebvre, Herve P | Unité de Recherche Clinique ; Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT) | Department of Companion Animal Clinical Sciences ; Norwegian School of Veterinary Science | Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT) | ToxAlim (ToxAlim) ; Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN) ; Institut National Polytechnique (Toulouse) (Toulouse INP) ; Université de Toulouse (UT)-Université de Toulouse (UT) | Departement Basic Sciences & Aquatic Medicine ; Norwegian School of Veterinary Science | Research Center ; Royal Canin
estimates of glomerular filtration rate (GFR) in dogs with various degrees of renal function. Animals—50 Great Anglo-Francais Tricolor Hounds with various degrees of renal function. Procedures—Boluses of iohexol (40 mg/kg) and creatinine (647 mg/kg) were injected IV. Blood samples were collected before administration and 5 and 10 minutes and 1, 2, 4, 6, and 8 hours after administration. Plasma creatinine and iohexol concentrations were assayed via an enzymatic method and high-performance liquid chromatography, respectively. A noncompartmental approach was used for pharmacokinetic analysis. Pharmacokinetic variables were compared via a Bland-Altman plot and an ANOVA. Results—Compared with results for creatinine, iohexol had a significantly higher mean ± SD plasma clearance (3.4 ± 0.8 mL/min/kg vs 3.0 ± 0.7 mL/min/kg) and a significantly lower mean volume of distribution at steady state (250 ± 37 mL/kg vs 539 ± 73 mL/kg), mean residence time (80 ± 31 minutes vs 195 ± 73 minutes), and mean elimination half-life (74 ± 20 minutes vs 173 ± 53 minutes). Despite discrepancies between clearances, especially for high values, the difference was < 0.6 mL/min/kg for 34 (68%) dogs. Three dogs with a low GFR (< 2 mL/min/kg) were classified similarly by both methods. Conclusions and Clinical Relevance—Plasma iohexol and creatinine clearances can be used interchangeably for screening patients suspected of having chronic kidney disease (ie, low GFR), but large differences may exist for dogs with a GFR within or above the reference range. (Am J Vet Res 2012;73:1841–1847)
Mostrar más [+] Menos [-]Effects of syringe type and storage conditions on results of equine blood gas and acid-base analysis Texto completo
2012
Kennedy, Sarah A. | Constable, Peter D. | Şen, İsmail | Couetil, Laurent
Objective: To determine effects of syringe type and storage conditions on blood gas and acid-base values for equine blood samples. Sample: Blood samples obtained from 8 healthy horses. Procedures: Heparinized jugular venous blood was equilibrated via a tonometer at 37°C with 12% O2 and 5% CO2. Aliquots (3 mL) of tonometer-equilibrated blood were collected in random order by use of a glass syringe (GS), general-purpose polypropylene syringe (GPPS), or polypropylene syringe designed for blood gas analysis (PSBGA) and stored in ice water (0°C) or at room temperature (22°C) for 0, 5, 15, 30, 60, or 120 minutes. Blood pH was measured, and blood gas analysis was performed; data were analyzed by use of multivariable regression analysis. Results: Blood Po2 remained constant for the reference method (GS stored at 0°C) but decreased linearly at a rate of 7.3 mm Hg/h when stored in a GS at 22°C. In contrast, Po2 increased when blood was stored at 0°C in a GPPS and PSBGA or at 22°C in a GPPS; however, Po2 did not change when blood was stored at 22°C in a PSBGA. Calculated values for plasma concentration of HCO3 and total CO2 concentration remained constant in the 3 syringe types when blood was stored at 22°C for 2 hours but increased when blood was stored in a GS or GPPS at 0°C. Conclusions and Clinical Relevance: Blood samples for blood gas and acid-base analysis should be collected into a GS and stored at 0°C or collected into a PSBGA and stored at room temperature.
Mostrar más [+] Menos [-]Effect of submaximal aerobic exercise on platelet function, platelet activation, and secondary and tertiary hemostasis in dogs Texto completo
2012
Bauer, Natali B. | Moritz, Andreas
Objective-To investigate whether submaximal aerobic exercise in dogs is followed by activation of all phases of coagulation as has been reported for humans. Animals-9 healthy Beagles. Procedures-30 minutes before dogs were exercised, a 16-gauge central venous catheter was placed in a jugular vein of each dog by use of the catheter-through-the-needle technique. Samples were collected before exercise, after running on a treadmill (6 km/h for 13 minutes), and at 60 minutes. Platelet activation was evaluated with platelet morphology indices (mean platelet component, mean platelet volume, and number of large platelets) provided by a laser-based hematology system. Platelet function was assessed in hirudin-anticoagulated whole blood with an impedance-based aggregometer with collagen as the agonist (final concentrations, 0, 1.6, 3.2, 5, and 10 micrograms/mL). Prothrombin time, activated partial thromboplastin time, and concentrations of fibrinogen, factor VIII, antithrombin, protein C, protein S, and fibrin D-dimer were determined automatically. Kaolin-activated thromboelastography variables R (reaction time), K (clot formation time), angle alpha, maximal amplitude, and G (clot stability) were measured in recalcified citrated whole blood. Results-Exercise resulted in a significant decrease in mean platelet volume and the number of large platelets but did not change the mean platelet component, which reflected platelet activation as well as platelet function. Secondary and tertiary coagulation did not change significantly, nor did thromboelastography variables. Conclusions and Clinical Relevance-Aerobic exercise resulted in a decrease in the number of large and thus most likely activated platelets but otherwise had no major impact on coagulation in dogs.
Mostrar más [+] Menos [-]Pharmacokinetics of a single intramuscular injection of ceftiofur crystalline-free acid in American black ducks (Anas rubripes) Texto completo
2012
Hope, Katharine L. | Tell, Lisa A. | Byrne, Barbara A. | Murray, Suzan | Wetzlich, Scott E. | Ware, Lisa H. | Lynch, Warren | Padilla, Luis R. | Boedeker, Nancy C.
Objective: To determine the pharmacokinetic properties of 1 IM injection of ceftiofur crystalline-free acid (CCFA) in American black ducks (Anas rubripes). Animals: 20 adult American black ducks (6 in a preliminary experiment and 14 in a primary experiment). Procedures: Dose and route of administration of CCFA for the primary experiment were determined in a preliminary experiment. In the primary experiment, CCFA (10 mg/kg, IM) was administered to ducks. Ducks were allocated into 2 groups, and blood samples were obtained 0.25, 0.5, 1, 2, 4, 8, 12, 48, 96, 144, 192, and 240 hours or 0.25, 0.5, 1, 2, 4, 8, 24, 72, 120, 168, and 216 hours after administration of CCFA. Plasma concentrations of ceftiofur free acid equivalents (CFAEs) were determined by use of high-performance liquid chromatography. Data were evaluated by use of a naive pooled-data approach. Results: The area under the plasma concentration versus time curve from 0 hours to infinity was 783 h•μg/mL, maximum plasma concentration observed was 13.1 μg/mL, time to maximum plasma concentration observed was 24 hours, terminal phase half-life was 32.0 hours, time that concentrations of CFAEs were higher than the minimum inhibitory concentration (1.0 μg/mL) for many pathogens of birds was 123 hours, and time that concentrations of CFAEs were higher than the target plasma concentration (4.0 μg/mL) was 73.3 hours. Conclusions and Clinical Relevance: On the basis of the time that CFAE concentrations were higher than the target plasma concentration, a dosing interval of 3 days can be recommended for future multidose CCFA studies.
Mostrar más [+] Menos [-]Effects of acepromazine maleate on platelet function assessed by use of adenosine diphosphate activated– and arachidonic acid– activated modified thromboelastography in healthy dogs Texto completo
2012
Conner, Bobbi J. | Hanel, Rita M. | Hansen, Bernard D. | Motsinger-Reif, Alison A. | Asakawa, Makoto | Swanson, Clifford R.
Objective: To evaluate the effect of acepromazine maleate administered IV on platelet function assessed in healthy dogs by use of a modified thromboelastography assay. Animals: 6 healthy adult mixed-breed dogs. Procedures: Dogs received each of 3 treatments (saline [0.9% NaCl] solution [1 to 2 mL, IV] and acepromazine maleate [0.05 and 0.1 mg/kg, IV]) in a randomized crossover study with a minimum 3-day washout period between treatments. From each dog, blood samples were collected via jugular venipuncture immediately before and 30 and 240 minutes after administration of each treatment. A modified thromboelastography assay, consisting of citrated kaolin–activated (baseline assessment), reptilase-ADP–activated (ADP-activated), and reptilase-arachidonic acid (AA)–activated (AA-activated) thromboelastography, was performed for each sample. Platelet inhibition was evaluated by assessing the percentage change in maximum amplitude for ADP-activated or AA-activated samples, compared with baseline values. Percentage change in maximum amplitude was analyzed by use of Skillings-Mack tests with significance accepted at a family-wise error rate of P < 0.05 by use of Bonferroni corrections for multiple comparisons. Results: No significant differences were found in the percentage change of maximum amplitude from baseline for ADP-activated or AA-activated samples among treatments at any time. Conclusions and Clinical Relevance: Platelet function in dogs, as assessed by use of a modified thromboelastography assay, was not inhibited by acepromazine at doses of 0.05 or 0.1 mg/kg, IV. This was in contrast to previous reports in which it was suggested that acepromazine may alter platelet function via inhibition of ADP and AA.
Mostrar más [+] Menos [-]Kaolin-activated thromboelastography in echocardiographically normal cats Texto completo
2012
Hall, Daniel J. | Rush, John E. | deLaforcade, Armelle M. | Shaw, Scott P.
Objective: To determine reference values for kaolin-activated thromboelastography in echocardiographically normal cats. Animals: 30 healthy cats without evidence of cardiomyopathy on echocardiographic examination. Procedures: All cats underwent echocardiographic examination, the findings of which were reviewed by a board-certified cardiologist. Cats that struggled (n = 10) received mild sedation with butorphanol and midazolam IM to permit phlebotomy without interruption in jugular venous blood flow. Blood samples were collected for analysis of thromboelastography variables, PCV, total solids concentration, platelet count, activated partial thromboplastin time, prothrombin time, fibrinogen concentration, and antithrombin concentration. Results: All 4 thromboelastography variables had < 5% mean intra-assay variability. Mean values were as follows: reaction time, 4.3 minutes; clotting time, 1.6 minutes; α angle, 66.5°; and maximum amplitude, 56.4 mm. Compared with nonsedated cats, cats that required sedation had a significantly shorter clotting time and greater α angle, whereas reaction time and maximum amplitude were not significantly different. Conclusions and Clinical Relevance: Kaolin-activated thromboelastography was a reliable test with unremarkable intra-assay variability in echocardiographically normal cats. Sedation may affect certain thromboelastography variables, but the effect is unlikely to be clinically important. It remains unknown whether subclinical cardiomyopathy has a significant effect on thromboelastography variables in cats.
Mostrar más [+] Menos [-]Daily endogenous cortisol production and hydrocortisone pharmacokinetics in adult horses and neonatal foals Texto completo
2012
Hart, Kelsey A. | Dirikolu, Levent | Ferguson, Duncan C. | Norton, Natalie A. | Barton, Michelle H.
Objective-To compare daily endogenous cortisol production rate and the pharmacokinetics of an IV bolus of hydrocortisone between neonatal foals and adult horses. Animals-10 healthy full-term 2- to 4-day-old foals and 7 healthy adult horses. Procedures-Blood samples were collected from each horse every 15 to 20 minutes for 24 hours for determination of 24-hour mean cortisol concentration. Afterward, dexamethasone (0.08 mg/kg) was administered IV to suppress endogenous cortisol production. Twelve hours afterward, hydrocortisone sodium succinate (1.0 mg/kg) was administered as a rapid IV bolus and serial blood samples were collected to determine hydrocortisone pharmacokinetics. Cortisol concentrations, daily cortisol production rate, and hydrocortisone pharmacokinetics were determined, and results were compared between adult horses and foals. Results-The mean +/- SD 24-hour cortisol concentration was significantly lower in foals (20 +/- 4 ng/mL) than in horses (26 +/- 6 ng/mL), but the daily cortisol production rate was significantly greater in foals (6,710 +/- 320 ng/kg/d) than in horses (2,140 +/- 400 ng/kg/d). For hydrocortisone, foals had a significantly greater volume of distribution at steady state (1.92 +/- 1.11 L/kg) and total body clearance (1.39 +/- 0.108 L/kg/h) and significantly lower peak plasma concentration (1,051 +/- 343 ng/mL) than did horses (0.58 +/- 0.15 L/kg, 0.349 +/- 0.065 L/kg/h, and 8,934 +/- 3,843 ng/mL, respectively). Conclusions and Clinical Relevance-Important differences were detected in cortisol production and metabolism between neonatal foals and adult horses consistent with lower plasma protein binding of cortisol in foals. This decrease may contribute to cortisol insufficiency during prolonged critical illness in neonatal foals.
Mostrar más [+] Menos [-]Detection of interferon-γ response to tuberculosis in blood collected at commencement of exsanguination at slaughter from cattle sensitized with Mycobacterium bovis Texto completo
2012
Okafor, Chika C. | Grooms, Dan | Bolin, Steven R. | Kaneene, John B.
Objective: To determine whether an interferon (IFN)-γ response sufficient to categorize cattle as positive for tuberculosis can be detected in blood collected at commencement of exsanguination at slaughter. Animals: 15 Holstein cows. Procedures: 12 cows were experimentally sensitized by SC injection with inactivated Mycobacterium bovis in mineral oil, which induced an immune response that mimicked natural infection with M bovis. Three nonsensitized control cows were injected SC with mineral oil alone. By 5 weeks after injection, only the 12 sensitized cows had positive results for tuberculosis with whole blood IFN-γ assay. At that time, all 15 cows were sent to slaughter and samples of blood were collected from each cow immediately before stunning and at commencement of exsanguination (within 90 seconds after stunning). A whole blood IFN-γ assay was performed on the samples. Conditional probability and paired t tests were used to analyze changes in the categorical test interpretation and qualitative IFN-γ production, respectively. Results: All 12 sensitized cows had positive results for tuberculosis in samples obtained immediately before stunning, and 9 retained positive results for samples obtained at commencement of exsanguination. There was a significant decrease in the mean background-corrected IFN-γ ELISA optical density values for samples obtained at commencement of exsanguination. Conclusions and Clinical Relevance: IFN-γ response sufficient to classify cattle as positive for tuberculosis could be detected in blood collected at commencement of exsanguination. These findings support further development and use of the IFN-γ assay on blood samples collected at exsanguination as part of a bovine tuberculosis surveillance program.
Mostrar más [+] Menos [-]Estimates of the pharmacokinetics of famciclovir and its active metabolite penciclovir in young Asian elephants (Elephas maximus) Texto completo
2012
Brock, A Paige | Isaza, Ramiro | Hunter, Robert P. | Richman, Laura K. | Koch, David E. | Schmitt, Dennia L. | Montali, Richard J. | Lindsay, William A.
Objective: To determine plasma pharmacokinetics of penciclovir following oral and rectal administration of famciclovir to young Asian elephants (Elephas maximus). Animals: 6 healthy Asian elephants (5 females and 1 male), 4.5 to 9 years old and weighing 1,646 to 2,438 kg. Procedures: Famciclovir was administered orally or rectally in accordance with an incomplete crossover design. Three treatment groups, each comprising 4 elephants, received single doses of famciclovir (5 mg/kg, PO, or 5 or 15 mg/kg, rectally); there was a minimum 12-week washout period between subsequent famciclovir administrations. Serial blood samples were collected after each administration. Samples were analyzed for famciclovir and penciclovir with a validated liquid chromatography–mass spectroscopy assay. Results: Famciclovir was tolerated well for both routes of administration and underwent complete biotransformation to the active metabolite, penciclovir. Mean maximum plasma concentration of penciclovir was 1.3 μg/mL at 1.1 hours after oral administration of 5 mg/kg. Similar results were detected after rectal administration of 5 mg/kg. Mean maximum plasma concentration was 3.6 μg/mL at 0.66 hours after rectal administration of 15 mg/kg; this concentration was similar to results reported for humans receiving 7 mg/kg orally. Conclusions and Clinical Relevance: Juvenile Asian elephants are susceptible to elephant endotheliotropic herpesvirus. Although most infections are fatal, case reports indicate administration of famciclovir has been associated with survival of 3 elephants. In Asian elephants, a dose of 8 to 15 mg of famciclovir/kg given orally or rectally at least every 8 hours may result in penciclovir concentrations that are considered therapeutic in humans.
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