ObjectiveTo investigate the volume kinetic between 2 crystalloid fluid bolus rates in anesthetized cats.DesignProspective, randomized, dose-response study.SettingUniversity laboratory.AnimalsTen convenience-sample, purpose-bred domestic shorthair and medium hair cats.InterventionsIntravenous 20 mL/kg balanced crystalloid fluid over 10 (G10) or 40 (G40) minutes under anesthesia in a randomized order with at least a 5-day washout period.Measurements and Main ResultsSerial measurements of hemoglobin (Hb) concentration and PCV were performed up to 60 minutes after conclusion of the fluid bolus. Plasma dilution was calculated with the Hb dilution method and fitted to a 2-compartment microconstant kinetic model using nonlinear mixed-effect models. The apparent central plasma volume (Vc) was similar between the 2 groups (G10: 81.2 +/- 23.8 mL/kg and G40: 78.8 +/- 10.2 mL/kg). The apparent peripheral volume (Vp) of G10 (4.81E+8 +/- 2.66E+8 mL/kg) was twice that of G40 (2.36E+8 +/- 6.44E+7 mL/kg). The rate constant from Vc to Vp (K12) of G10 (0.057 +/- 0.0196/min) was almost twice that of G40 (0.0302 +/- 0.00807/min). The elimination constant of G10 (0.0113 +/- 0.00672/min) was almost twice that of G40 (0.00534 +/- 0.00279/min). The peak plasma expansion was similar between G10 and G40 (20.7 +/- 1.9 and 19.1 +/- 5.1 mL/kg). Area under the curve for plasma dilution versus time of the first 90 minutes from the beginning of the boluses was not statistically different between G10 and G40.ConclusionsThe volume expansion over time was not different likely due to the slow elimination. The plasma dilution to crystalloid bolus between subjects is varied in anesthetized cats. Clinicians should consider the slow elimination and return of crystalloid fluid from the Vp to Vc when prescribing fluid therapy in anesthetized cats.

Nine horses received 20 mg/kg of intravenous ( LEV IV ); 30 mg/kg of intragastric, crushed immediate release ( LEV CIR ); and 30 mg/kg of intragastric, crushed extended release ( LEV CER ) levetiracetam, in a three‐way randomized crossover design. Crushed tablets were dissolved in water and administered by nasogastric tube. Serum samples were collected over 48 hr, and levetiracetam concentrations were determined by immunoassay. Mean ± SD peak concentrations for LEV CIR and LEV CER were 50.72 ± 10.60 and 53.58 ± 15.94 μg/ml, respectively. The y ‐intercept for IV administration was 64.54 ± 24.99 μg/ml. The terminal half‐life was 6.38 ± 1.97, 7.07 ± 1.93 and 6.22 ± 1.35 hr for LEV CIR , LEV CER , and LEV IV , respectively. Volume of distribution at steady‐state was 630 ± 73.4 ml/kg. Total body clearance after IV administration was 74.40 ± 19.20 ml kg −1 hr −1 . Bioavailability was 96 ± 10, and 98 ± 13% for LEV CIR and LEV CER , respectively. A single dose of Levetiracetam ( LEV ) was well tolerated. Based on this study, a recommended dosing regimen of intravenous or oral LEV of 32 mg/kg every 12 hr is likely to achieve and maintain plasma concentrations within the therapeutic range suggested for humans, with optimal kinetics throughout the dosing interval in healthy adult horses. Repeated dosing and pharmacodynamic studies are warranted.

Currently, there are no legal treatments in the United States for cattle infected with Tritrichomonas foetus. This obligate parasite of the reproductive tract of the bovid creates serious economic loss in the cattle industry in the United States. The hypothesis of this study was that benzimidazoles (oxibendazole or oxfendazole) or ponazuril combined with a polymer enhancer, specifically polymer lecithin organogel (PLO), in a topical formulation may be an effective treatment for bulls infected with r foetus. Three in vitro experiments were performed to evaluate the antiprotozoal effects of the benzimidazole and ponazuril formulations, and all involved components on the growth of r foetus organisms.

Edmondson, M. A., Duran, S. H., Boothe, D. M., Stewart, A. J., Ravis, W. R. Pharmacokinetics of tramadol and its major metabolites in alpacas following intravenous and oral administration. J. vet. Pharmacol. Therap. 35 , 389–396. Tramadol, a centrally acting opioid analgesic with monamine reuptake inhibition, was administered to six alpacas (43–71 kg) randomly assigned to two treatment groups, using an open, single‐dose, two‐period, randomized cross‐over design at a dose of 3.4–4.4 mg/kg intravenously (IV) and, after a washout period, 11 mg/kg orally. Serum samples were collected and stored at −80 °C until assayed by HPLC. Pharmacokinetic parameters were calculated. The mean half‐lives ( t 1/2 ) IV were 0.85 ± 0.463 and 0.520 ± 0.256 h orally. The Cp(0) IV was 2467 ± 540 ng/mL, and the C max was 1202 ± 1319 ng/mL orally. T max occurred at 0.111 ± 0.068 h orally. The area under the curve (AUC 0 ‐∞ ) IV was 895 ± 189 and 373 ± 217 ng*h/mL orally. The volume of distribution ( V d[area] ) IV was 5.50 ± 2.66 L/kg. Total body clearance (Cl) IV was 4.62 ± 1.09 h; Cl/F for oral administration was 39.5 ± 23 L/h/kg. The IV mean residence time (MRT) was 0.720 ± 0.264. Oral adsorption ( F ) was low (5.9–19.1%) at almost three times the IV dosage with a large inter‐subject variation. This may be due to binding with the rumen contents or enzymatic destruction. Assuming linear nonsaturable pharmacokinetics and absorption processes, a dosage of 6.7 times orally would be needed to achieve the same IV serum concentration of tramadol. The t 1/2 of all three metabolites was longer than the parent drug; however, O ‐DMT, N ‐DMT, and Di‐DMT metabolites were not detectable in all of the alpacas. Because of the poor bioavailability and adverse effects noted in this study, the oral administration of tramadol in alpacas cannot be recommended without further research.

The purpose of this study was to evaluate the pharmacokinetics of ketamine in mature Holstein cows following administration of a single intravenous (i.v.) dose. Plasma and milk concentrations were determined using a high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following i.v. administration, plasma T(max) was 0.083 h and plasma C(max) was 18,135 ± 22,720 ng/mL. Plasma AUC was 4484 ± 1,398 ng·h/mL. Plasma t(½β) was 1.80 ± 0.50 h and mean residence time was 0.794 ± 0.318 h with total body clearance of 1.29 ± 0.70 L/h/kg. The mean plasma steady-state volume of distribution was calculated as 0.990 ± 0.530 L/kg and volume of distribution based on area was calculated as 3.23 ± 1.51 L/kg. The last measurable time for ketamine detection in plasma was 8.0 h with a mean concentration of 24.9 ± 11.8 ng/mL. Milk T(max) was detected at 0.67 ± 0.26 h with C(max) of 2495 ± 904 ng/mL. Milk AUC till the last time was 6593 ± 2617 ng·h/mL with mean AUC milk to AUC plasma ratio of 1.99 ± 2.15. The last measurable time that ketamine was detected in milk was 44 ± 10.0 h with a mean concentration of 16.0 ± 9.0 ng/mL.

The purpose of this study was to assess safety and alterations in body fluid concentrations of voriconazole in normal horses on days 7 and 14 following once daily dose of 4 mg/kg of voriconazole orally for 14 days. Body fluid drug concentrations were determined by the use of high performance liquid chromatography (HPLC). On day 7, mean voriconazole concentrations of plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, epithelial lining fluid (ELF), and urine were 1.47 +/- 0.63, 0.61 +/- 0.22, 0.70 +/- 0.20, 0.62 +/- 0.26, 0.55 +/- 0.32, 79.45 +/- 69.4, and 1.83 +/- 0.44 microg/mL respectively. Mean voriconazole concentrations in the plasma, peritoneal, synovial and cerebrospinal fluids, aqueous humor, ELF and urine on day 14 were 1.60 +/- 0.37, 1.02 +/- 0.27, 0.86 +/- 0.25, 0.64 +/- 0.21, 0.68 +/- 0.13, 47.76 +/- 45.4 and 3.34 +/- 2.17 respectively. Voriconazole concentrations in the bronchoalveolar cell pellet were below the limit of detection. There was no statistically significant difference between voriconazole concentrations of body fluids when comparing days 7 and 14. Results indicated that voriconazole distributes widely into body fluids.

The purpose of this study was to investigate the stereospecific pharmacokinetics of ketorolac (KT) in goats following a single 2 mg/kg intravenous (i.v.) dose and a single 6 mg/kg oral dose. A stereoselective high pressure liquid chromatography assay was used to quantify ketorolac plasma concentrations. Pharmacokinetic parameters for both stereoisomers were estimated by model independent methods. Following an i.v. dose, the plasma concentration profiles for the stereoisomers were similar with half-lives of 1.05 +/- 0.62 h for R-KT and 1.05 +/- 0.61 h for S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.53 +/- 0.23 and 0.54 +/- 0.23 L.h/kg, respectively. Following an oral dose, the terminal half-lives were longer with values of 34.08 +/- 11.81 and 33.97 +/- 12.19 h for R-KT and S-KT, respectively. The average bioavailability was 133 +/- 23% for R-KT and S-KT, respectively. The longer half-lives and high apparent bioavailability after oral dosing are suggestive of a slow absorption process in the gastrointestinal tract and recycling. The results indicate that interconversion of the stereoisomers of ketorolac is absent in goats. However, studies with individual isomers are needed before any conclusion can be drawn about the lack of bioinversion.

Voriconazole is a new antifungal drug that has shown effectiveness in treating serious fungal infections and has the potential for being used in large animal veterinary medicine. The objective of this study was to determine the plasma concentrations and pharmacokinetic parameters of voriconazole after single-dose intravenous (i.v.) and oral administration to alpacas. Four alpacas were treated with single 4 mg/kg i.v. and oral administrations of voriconazole. Plasma voriconazole concentrations were measured by a high-performance liquid chromatography method. The terminal half-lives following i.v. and oral administration were 8.01 +/- 2.88 and 8.75 +/- 4.31 h, respectively; observed maximum plasma concentrations were 5.93 +/- 1.13 and 1.70 +/- 2.71 microg/mL, respectively; and areas under the plasma concentration vs. time curve were 38.5 +/- 11.1 and 9.48 +/- 6.98 mg.h/L, respectively. The apparent systemic oral availability was low with a value of 22.7 +/- 9.5%. The drug plasma concentrations remained above 0.1 microg/mL for at least 24 h after single i.v. dosing. The i.v. administration of 4 mg/kg/day voriconazole may be a safe and appropriate option for antifungal treatment of alpacas. Due to the low extent of absorption in alpacas, oral voriconazole doses of 20.4 to 33.9 mg/kg/day may be needed.

Phenylbutazone (PBZ) is a nonsteroidal anti-inflammatory drug used in the treatment of chronic pain and arthritis. Topical and transdermal administration of PBZ would be beneficial in large animals in terms of minimizing gastro-intestinal ulcerations and other side effects, easy administration to legs and joints and minimizing the dose to reduce systemic toxicity of the drug. A topical liposomal preparation with different concentrations of a mono-substituted alkyl amide (MSA) and PBZ was formulated. The formulations were evaluated by in vitro skin-permeation kinetics through deer skin using Franz diffusion cells. By increasing drug loading from 1% to 5% w/w, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Similarly, by increasing the MSA concentration from 0% to 4%, the steady-state flux (microg/cm(2)/h) of PBZ was increased twofold (P < 0.001). Overall, by increasing the drug load and the use of an appropriate amount of the penetration enhancer, the steady-state flux of PBZ through skin was increased fourfold (P < 0.001). MSA at both 2% and 4% w/w concentrations significantly increased the skin levels of PBZ as compared with control (P < 0.05). In conclusion, MSA served as an effective skin-penetration enhancer in the liposomal gel of PBZ for deer.

The purpose of this study was to evaluate the pharmacokinetics of lidocaine in mature Holstein cows following an inverted L and caudal epidural nerve block. Plasma and milk concentrations were determined using high-performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following administration via inverted L nerve block, serum T(max) was 0.521 +/- 0.226 h and serum C(max) was 572 +/- 207 ng/mL. Serum AUC was 1348 +/- 335 ng.h/mL. Apparent serum t((1/2)beta) was 4.19 +/- 1.69 h and MRT was 5.13 +/- 2.33 h with clearance uncorrected for the extent of absorption of 2.75 +/- 0.68 L/kg/h. The last measurable time of lidocaine detection in serum was 8.5 +/- 1.4 h with a mean concentration of 51 +/- 30 ng/mL. Milk T(max) was detected at 1.75 +/- 0.46 h with C(max) of 300 +/- 139 ng/mL. Milk AUC till the last time was 1869 +/- 450 ng.h/mL with the mean AUC milk to AUC serum ratio of 1.439 +/- 0.374. The last measurable time of lidocaine detection in milk was 32.5 +/- 16.2 h with a mean concentration of 46 +/- 30 ng/mL. There was no detectable lidocaine concentration in any samples following caudal epidural administration.

The purpose of this study was to establish the stereospecific pharmacokinetics of ketorolac (KT) in calves following a single 2 mg/kg intravenous (i.v.) and a single 8 mg/kg oral dose. Plasma concentrations were determined using a stereoselective HPLC assay. Pharmacokinetic parameters for both the stereoisomers were estimated by model-independent methods. Following an i.v. dose, the plasma concentration profiles of the stereoisomers were similar with half-lives of 5.9 +/- 5.1 h for R-KT and 6.0 +/- 4.9 h for S-KT. Clearance values for R- and S-KT after an i.v. dose were 0.0470 +/- 0.0370 and 0.0480 +/- 0.0370 L/h/kg respectively. After an oral dose, the terminal half-lives were longer than following i.v. administration with values of 14.77 +/- 3.08 and 14.55 +/- 2.95 h for R-KT and S-KT respectively. The average oral bioavailability was 86.5 +/- 20.6% for R-KT and 86.7 +/- 20.3% for S-KT. The results indicate that the stereoisomers of KT have similar pharmacokinetic profiles in calves. Although, unlike humans, bioinversion between KT stereoisomers appears minimal in calves, studies with individual isomers are needed before any firm conclusions can be drawn about this lack of KT bioinversion.

OBJECTIVE:To evaluate the cardiopulmonary and clinicopathologic effects of rapid IV administration of dimethyl sulfoxide (DMSO) in awake and halothane-anesthetized horses.DESIGN:Prospective study.ANIMALS:6 adult horses.PROCEDURES:Horses received IV infusion of 5 L of a balanced electrolyte solution with and without 1 g/kg (0.45 g/lb) of 10% DMSO solution when they were awake and anesthetized with halothane (4 treatments/horse). Arterial and venous blood samples were collected immediately before and at intervals during or after fluid administration and analyzed for blood gases and hematologic and serum biochemical variables, respectively. Heart rate, respiratory rate, and arterial blood pressure variables were recorded prior to, during, and after fluid administration.RESULTS:After administration of fluid with or without DMSO, changes in measured variables were detected immediately, but most variables returned to baseline values within 4 hours. One awake control horse had signs of anxiety; agitation and tachycardia were detected in 2 awake horses administered DMSO. These clinical signs disappeared when the rate of infusion was reduced. In anesthetized horses, increased concentrations of WBCs and plasma fibrinogen and serum creatine kinase activity persisted for 24 hours, which was related to the stress of anesthesia more than the effects of fluid administration.CONCLUSIONS AND CLINICAL RELEVANCE:Infusion of 5 L of balanced electrolyte solution with or without 10% DMSO induced minimal changes in cardiopulmonary function and clinicopathologic variables in either awake or halothane-anesthetized horses. Stress associated with anesthesia and recovery had a greater influence on measured variables in anesthetized horses than fluid administration.

Selenium (Se) deficiency disease has been described in camelids and only clinical data is available for administration of parenteral Se supplements. This study investigated the pharmacokinetic effects of subcutaneous Se injection (0.1 mg/kg) in llamas fed a diet adequate in Se. Absorption of Se was rapid with peak whole blood Se concentration at the first sampling time. Significant differences in whole blood Se concentration from before injection of Se were not found past 2 days after Se injection. Parenteral Se is unlikely to have a long-term effect on whole blood Se concentration in llamas fed adequate dietary Se.

Journal of Veterinary Pharmacology and TherapeuticsVolume 24, Issue 3 p. 227-231 Pharmacokinetics of phenylbutazone in llamas following single intravenous and oral doses C. B. Navarre, C. B. Navarre Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this authorW. R. Ravis, W. R. Ravis Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorR. Nagilla, R. Nagilla Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorA. Simpkins, A. Simpkins Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this authorS. H. Duran, S. H. Duran Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this authorD. G. Pugh, D. G. Pugh Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this author C. B. Navarre, C. B. Navarre Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this authorW. R. Ravis, W. R. Ravis Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorR. Nagilla, R. Nagilla Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorA. Simpkins, A. Simpkins Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this authorS. H. Duran, S. H. Duran Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this authorD. G. Pugh, D. G. Pugh Department of Large Animal Surgery and Medicine, Auburn University, AL 36849, USA.Search for more papers by this author First published: 21 December 2001 https://doi.org/10.1046/j.1365-2885.2001.00324.xCitations: 17 NAVARRE E-mail: [email protected] Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat References 1 Aerken, D.F. & Sans, R.A. (1985) Inhibitory effects of intravenous chloramphenicol sodium succinate on the disposition of phenylbutazone in horses. Journal of Pharmacokinetics and Biopharmacuetics, 13 , 467–476. 2 De Backer, P., Braeckman, R., Belpaire, F., Debackere, M. (1980) Bioavailability and pharmacokinetics of phenylbutazone in the cow. Journal of Veterinary Pharmacology and Therapeutics, 2 , 29–33. 3 Cheng, Z., McKellar, Q.A., Nolan, A., Lees, P. (1996) Pharmacokinetics and pharmacodynamics of phenylbutazone and oxyphenbutazone in the donkey. Journal of Veterinary Pharmacology and Therapeutics, 19 , 149–151. 4 Cheng, Z., Welsh, E., Nolan, A., McKellar, Q.A. (1997) Pharmacokinetic and pharmacodynamic studies on phenylbutazone and oxyphenbutazone in goats. Veterinary Record, 140 , 40–43. 5 Christensen, J.M., Smith, B.B., Murdane, S.B., Hollingshead, N. (1996) The disposition of five therapeutically important antimicrobial agents in llamas. Journal of Veterinary Pharmacology and Therapeutics, 19 , 431–438. 6 Dowling, P.M., Ferguson, J.G., Gibney, R.F. (1995) Pharmacokinetics of gentamicin in llamas. Proceedings of the American College of Veterinary Internal Medicine, 1031 (Abstract). 7 Ebel, S. (1989) The llama industry in the United States. Veterinary Clinics of North America: Food Animal, 5 , 1–20. 8 Eberhardson, B., Olsson, G., Applegrew, L.E., Jacobson, S. (1979) Pharmacokinetic studies of phenylbutazone in cattle. Journal of Veterinary Pharmacology and Therapeutics, 2 , 31–37. 9 Eltom, S.E., Guard, C.L., Schwark, W.S. (1993) The effect of age on phenylbutazone pharmacokinetics, metabolism and plasma protein binding in goats. Journal of Veterinary Pharmacology and Therapeutics, 16 , 141–151. 10 Kadir, A., Ali, B.H., Hadrami, G.A., Bashir, A.K., Landoni, M.F., Lees, P. (1997) Phenylbutazone pharmacokinetics and bioavailability in the dromedary camel (Camelus dromedarius). Journal of Veterinary Pharmacology and Therapeutics, 20 , 54–60. 11 Kopcha, M. & Ahl, A.S. (1989) Experimental uses of flunixin meglumine and phenylbutazone in food-producing animals. Journal of the American Veterinary Medical Association, 194 , 45–49. 12 Lackey, M.N., Belknap, E.B., Greco, D.S., Fettman, M.J. (1996) Single intravenous and multiple dose phamacokinetics of gentamicin in healthy llamas. American Journal of Veterinary Research, 57 , 1193–1199. 13 Lees, P. & Higgins, A.J. (1985) Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse. Equine Veterinary Journal, 17 , 83–96. 14 Lees, P. & Higgins, A.J. (1986) Effects of phenylbutazone paste in ponies: model of acute nonimune inflammation. American Journal of Veterinary Research, 11 , 2359–2363. 15 Lees, P., Taylor, J.B.O., Higgins, A.J., Sharma, S.C. (1986) Phenylbutazone and oxphenbutazone distribution into tissue fluids in the horse. Journal of Veterinary Pharmacology and Therapeutics, 9 , 204–212. 16 Lees, P., Ayliffe, T., Maitho, T.E., Taylor, J.B.O. (1988a) Pharmacokinetics, metabolism and excretion of phenylbutazone in cattle following intravenous, intramuscular and oral administration. Research in Veterinary Science, 44 , 57–67. 17 Lees, P., Taylor, J.B.O., Higgins, A.J., Sedgwick, A.D. (1988b) In vitro and in vivo binding of phenlbutazone and related drugs to equine feeds and digesta. Research in Veterinary Science, 44 , 50–56. 18 Levy, R.A. & Smith, D.L. (1989) Clinical differences among nonsteroidal anti-inflammatory drugs: implications for therapeutic subsitution in ambulatory patients. DICP, The Annals of Pharmacotherapy, 23 , 76–85. 19 MacAllister, C.G. (1994) Nonsteroidal anti-inflammatory drugs: their mechanism of action and clinical uses in horses. Veterinary Medicine, 89 , 237–240. 20 MacAllister, C.G. & Taylor-MacAllister, C. (1994) Treating and preventing the adverse effects of nonsteroidal anti-inflammatory drugs in horses. Veterinary Medicine, 89 , 241–246. 21 MacAllister, C.G., Morgan, S.J., Borne, A.T., Pollet, R.A. (1993) Comparison of adverse effects of phenylbutazone, flunixin meglumine and ketoprofen in horses. Journal of the American Veterinary Medical Association, 202 , 71–77. 22 Maitho, T.E., Lees, P., Taylor, J.B. (1985) Absorption and pharmacokinetics of phenylbutazone in Welsh Mountain ponies. Journal of Veterinary Pharmacology and Therapeutics, 9 , 26–39. 23 Mealey, K.L., Matthews, N.S., Peck, K.E., Ray, A.C., Taylor, T.S. (1997) Comparative pharmacokinetics of phenylbutazone and its metabolite oxyphenbutazone in clinically normal horses and donkeys. American Journal of Veterinary Research, 58 , 53–55. 24 Rubsamen, K. & Engelhardt, W.V. (1975) Water metabolism in the llama. Comparative Biochemistry and Physiology, 52A , 595–598. 25 Rubsamen, K. & Engelhardt, W. (1978) Bicarbonate secretion and solute absorption in forestomach of the llama. American Journal of Physiology, 235 , E1–E6. 26 Rubsamen, K. & Engelhardt, W. (1979) Morphological and functional peculiarities of the llama forestomach. Annales de Recherche Veterinaires Journal, 10 , 473–475. 27 Soma, L.R., Gallis, D.E., Davis, B.A., Cochran, T.A., Woodward, C.B. (1983) Phenylbutazone kinetics and metabolite concentrations in the horse after five days. American Journal of Veterianry Research, 44 , 2104–2109. 28 Vallenas, A.P. & Stevens, C.E. (1971) Motility of the llama and guanaco stomach. American Journal of Physiology, 220 , 275–282. 29 Williams, R.J., Smith, J.A., Boudinot, F.D., Knight, A.P. (1990) Pharmacokinetics of phenylbutazone given intravenously or orally in mature Holstein bulls. American Journal of Veterinary Research, 51 , 367–370. Citing Literature Volume24, Issue3June 2001Pages 227-231 ReferencesRelatedInformation

Journal of Veterinary Pharmacology and TherapeuticsVolume 24, Issue 3 p. 223-226 Stereoselective pharmacokinetics of ketoprofen in llamas following intravenous administration C. B. Navarre, C. B. Navarre Department of Large Animal Surgery and Medicine, Auburn University, AL, USASearch for more papers by this authorW. R. Ravis, W. R. Ravis Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorJ. Campbell, J. Campbell Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorR. Nagilla, R. Nagilla Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorS. H. Duran, S. H. Duran Department of Large Animal Surgery and Medicine, Auburn University, AL, USASearch for more papers by this authorD. G. Pugh, D. G. Pugh Department of Large Animal Surgery and Medicine, Auburn University, AL, USASearch for more papers by this author C. B. Navarre, C. B. Navarre Department of Large Animal Surgery and Medicine, Auburn University, AL, USASearch for more papers by this authorW. R. Ravis, W. R. Ravis Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorJ. Campbell, J. Campbell Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorR. Nagilla, R. Nagilla Department of Pharmacal Sciences, Auburn University, AL 36849, USA.Search for more papers by this authorS. H. Duran, S. H. Duran Department of Large Animal Surgery and Medicine, Auburn University, AL, USASearch for more papers by this authorD. G. Pugh, D. G. Pugh Department of Large Animal Surgery and Medicine, Auburn University, AL, USASearch for more papers by this author First published: 21 December 2001 https://doi.org/10.1046/j.1365-2885.2001.00321.xCitations: 14 NAVARRE Department of Large Animal Surgery and Medicine, Auburn University, AL, USA Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume24, Issue3June 2001Pages 223-226 RelatedInformation

The objective of this study was to evaluate the efficacy of regional intravenous (i.v.) injection of ceftiofur in delivery of this drug to joint fluid and plasma in a limb distal to a tourniquet in five, healthy, adult, mixed breed beef cattle. A tourniquet was positioned in the mid-metacarpal region, and 500 mg of ceftiofur was administered through a catheter in the dorsal common digital vein (DCDV). Plasma samples were collected from the catheter at 15, 30 and 45 min postinjection, and from the abaxial proper palmar vein (APPV) at 15 min postinjection. Synovial fluid was collected from the metacarpal phalangeal joint at 45 min postinjection. Ceftiofur concentrations were estimated in plasma and synovial fluid using high-pressure liquid chromatography (HPLC) and a microbiological assay utilizing Pasteurella haemolytica as the test organism. Both assays indicated highest plasma concentrations of ceftiofur at 15 min, with the concentrations declining with time. Concentrations of ceftiofur in plasma obtained from the DCDV were not significantly different from APPV levels, indicating rapid distribution of ceftiofur within the limb. Microbiological assay always demonstrated higher concentrations of ceftiofur compared with HPLC assay, because the former probably also detected the active metabolites of ceftiofur as well as the parent compound. At 45 min, ceftiofur concentrations determined by HPLC were 251+/-97 and 15+/-5 microg/mL in plasma and synovial fluid, respectively. Regional intravenous injection appears to be a feasible technique to produce rapid distribution of ceftiofur within the limb well above therapeutic concentrations.

OBJECTIVE:To determine intravascular and intrasynovial pharmacokinetics of the R and S enantiomers of ketoprofen after i.v. and i.m. administration to horses.ANIMALS:6 healthy adult mares.PROCEDURE:Horses were weighed and ketoprofen (2.2 mg/kg of body weight) was administered i.v. Blood and synovial fluid samples were obtained and analyzed for concentrations of the R and S enantiomers by means of a modified reverse-phase stereospecific high-pressure liquid chromatographic method. Three weeks later, the procedure was repeated, except that ketoprofen was given IM. Protein binding of ketoprofen enantiomers was determined by means of ultrafiltration. Nonlinear least squares methods were used to calculate pharmacokinetic parameters.RESULTS:Data obtained after i.v. administration best fit an open, two-compartment model. Mean +/- SD S-to-R serum concentration ratios after i.v. and i.m. administration were 1.36 +/- 0.214 and 1.34 +/- 0.245, respectively. Intrasynovial concentrations of the R and S enantiomers of ketoprofen could be measured for only the first 3 hours after i.v. administration; concentrations were less than the limit of quantification by 4 hours after i.v. administration and at all times after i.m. administration. Extent of protein binding of the R enantiomer was not significantly different from extent of protein binding of the S enantiomer; extent of protein binding did not appear to be concentration dependent. Mean free S-to-free R serum concentration ratios, adjusted for protein binding, after i.v. and i.m. administration were 1.58 and 1.56, respectively.CONCLUSIONS:The R and S enantiomers of ketoprofen are rapidly absorbed and eliminated, have low volumes of distribution, and are highly protein bound.

The pharmacokinetics of ciprofloxacin was investigated in healthy, mature ponies. Ciprofloxacin was administered intravenously to six ponies at a dose of 5 mg per kg body weight. Seven days later, ciprofloxacin was administered orally to each pony at the same dose. Intravenous ciprofloxacin concentration vs. time data best fit a two-compartment open model with first-order elimination from the central compartment. Mean plasma half-life, based on the terminal phase, was 157.89 min (harmonic mean). Total body clearance of ciprofloxacin was 18.12 +/- 3.99 mL/min/kg. Volume of distribution at steady-state was 3.45 +/- 0.72 L/kg. From the pharmacokinetic data and reported minimum inhibitory concentrations for equine gram-negative pathogens, the appropriate dosage of ciprofloxacin was determined to be 5.32 mg per kg body weight at 12 h intervals. Bioavailability of oral ciprofloxacin in ponies was 6.8 +/- 5.33%. Owing to the poor bioavailability, a dosage regimen could not be proposed for oral ciprofloxacin administration in horses. Ciprofloxacin concentrations were determined in tissues and body fluids at 1, 2 and 4 h after intravenous administration. At all times, tissue concentrations exceeded plasma concentrations of ciprofloxacin. Highest concentrations were achieved in kidneys and urine. Potentially therapeutic concentrations were obtained in cerebrospinal and joint fluid, but low concentrations were achieved in aqueous humour.

Because caffeine is metabolized by the hepatic P-450 cytochrome oxidase system, clearance of caffeine is an excellent quantitative test of hepatic function in human beings. It is currently used in much the same way that creatinine clearance is used to assess renal function. Caffeine clearance was measured in lactating dairy cows initially to determine the suitability of caffeine clearance as an indicator of hepatic function in cattle. Pharmacokinetic variables of caffeine were studied in 6 adult lactating dairy cows after i.v. administration of a single dose of caffeine sodium benzoate (2 mg of caffeine/kg of body weight). Caffeine concentration was analyzed by use of an automated enzyme immunoassay. The lower limit of detection of the assay for caffeine in serum was 0.079 micrograms/ml. Serum caffeine concentration-time curves best fit an open two-compartment pharmacokinetic model. Harmonic mean elimination half-life was 3.8 (range, 2.6 to 6.9) hours, and total clearance was 0.118 (range, 0.090 to 0.197) L/kg/h. Milk caffeine concentration was similar to serum concentration 1.5 to 24 hours after caffeine administration. Adverse effects were not observed in cows given caffeine.