Pharmacokinetics and ex vivo pharmacodynamics of cefquinome in porcine serum and tissue cage fluids

A tissue cage (TC) model was used to evaluate the pharmacokinetics and ex vivo pharmacodynamics of cefquinome after intravenous (IV) and intramuscular (IM) administration to piglets at 2 mg/kg bodyweight. The mean values of area under the concentration–time curve (AUC) were 21.28 (IV) and 21.37 (IM) μg h/mL for serum, and 17.40 (IV) and 16.57 (IM) μg h/mL for TC fluid (TCF), respectively. Values of maximum concentration (C_max) were 6.15 μg/mL (serum) and 1.15 μg/mL (TCF) after IM administration. The elimination half-lives (t_1/2β) in TCF (10.63 h IV and 11.81 h IM) were significantly higher than those in serum (2.33 h IV and 2.30 h IM) (P < 0.05). The values of AUC_TCF/AUC_serum (%) after IV and IM administration were 82.4% and 80.7%, respectively.The ex vivo time-kill curves were established for serum and TCF samples using Escherichia coli ATCC 25922. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration values of cefquinome against E. coli were 0.030 and 0.060 μg/mL in Mueller–Hinton broth, and 0.032 and 0.064 μg/mL in both serum and TCF, respectively. The ex vivo growth inhibition data of TCF after IM administration were fitted to the sigmoid E_max model; AUC_24h/MIC was 35.01 h for bactericidal activity and 44.28 h for virtual eradication, respectively. The findings from this study suggest that cefquinome may be therapeutically effective in diseases of pigs caused by E. coli when used at a dose rate of 1.33 mg/kg administered every 24 h for organisms with MIC₉₀ ⩽ 0.50 μg/mL.     

Antinociceptive efficacy and plasma concentrations of transdermal buprenorphine in dogs

To assess the antinociceptive efficacy of transdermal (TD) buprenorphine (B) in dogs, a prospective, positive-controlled experimental study was performed in 10 healthy Beagles. In an open label crossover design, the dogs initially received intravenous B (IVB, 0.02 mg kg^?1) as a positive control, followed by TDB (52.5 μg h^?1) 4 months later. Blood was collected at regular intervals for determination of the plasma concentrations of B ([B]) and its metabolite norbuprenorphine. The antinociceptive efficacy was assessed using thermal and mechanical models of nociception. The peak concentration [B] was 1.54 ng mL^?1 (±1.98) 60 h after TDB application, although three dogs had no measurable [B] after TDB. Maximum thermal threshold (TT) was 52.6 °C (±0.48) at 1 h after IVB administration and 51.63 °C (±1.01) 72 h after TDB application. The significant increase in TT indicated that effective antinociception was achieved beyond 36 h after the application of TDB, lasting until patch removal. There was hysteresis between [B] and the antinociceptive effect.     

Pharmacokinetics of erythromycin after intravenous,intramuscular and oral administration to cats

The aim of this study was to characterise the pharmacokinetic properties of different formulations of erythromycin in cats. Erythromycin was administered as lactobionate (4 mg/kg intravenously (IV)), base (10 mg/kg, intramuscularly (IM)) and ethylsuccinate tablets or suspension (15 mg/kg orally (PO)). After IV administration, the major pharmacokinetic parameters were (mean ± SD): area under the curve (AUC)_(0–∞) 2.61 ± 1.52 μg h/mL; volume of distribution (V_z) 2.34 ± 1.76 L/kg; total body clearance (Cl_t) 2.10 ± 1.37 L/h kg; elimination half-life (t_½λ) 0.75 ± 0.09 h and mean residence time (MRT) 0.88 ± 0.13 h. After IM administration, the principal pharmacokinetic parameters were (mean ± DS): peak concentration (C_max), 3.54 ± 2.16 μg/mL; time of peak (T_max), 1.22 ± 0.67 h; t_½λ, 1.94 ± 0.21 h and MRT, 3.50 ± 0.82 h. The administration of erythromycin ethylsuccinate (tablets and suspension) did not result in measurable serum concentrations. After IM and IV administrations, erythromycin serum concentrations were above minimum inhibitory concentration (MIC)₉₀ = 0.5 μg/mL for 7 and 1.5 h, respectively. However, these results should be interpreted cautiously since tissue erythromycin concentrations have not been measured and can reach much higher concentrations than in blood, which may be associated with enhanced clinical efficacy.     

Pharmacokinetics of dexamethasone after intravenous and intramuscular administration in broiler chickens

The aim of this study was to determine the pharmacokinetics of dexamethasone in broiler chickens. Dexamethasone sodium phosphate (0.3 mg/kg bodyweight) was injected IV or IM and blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 2, 4, 6, 8, 10, 12 and 24 h after administration. Dexamethasone in the plasma samples was measured using a liquid chromatography–tandem mass spectrometry method and the pharmacokinetics analysed according to a one-compartmental model.The maximum plasma concentration after IM administration occurred at 0.37 h. The elimination half-life for dexamethasone was 0.46 h and 0.70 h following IV and IM administration, respectively, which was shorter than other species, while the clearance (1.26 L/h kg) was higher than has been reported for other species (<0.5 L/h kg). The volume of distribution (～1 L/kg) was similar to values reported for other species and the bioavailability of dexamethasone after IM administration was 100%. The results from this study will be useful in investigating whether inflammatory disease may affect the pharmacokinetic parameters of dexamethasone in chickens.     

Plasma concentrations of buprenorphine after epidural administration in conscious cats

Buprenorphine plasma concentrations were measured after administering buprenorphine (20 μg/kg) into the lumbosacral epidural space of conscious cats chronically instrumented with an epidural catheter. Blood was collected from a jugular vein before injection and 15, 30, 45 and 60 min and 2, 3, 4, 5, 6, 8, 12 and 24 h after administration. Plasma buprenorphine concentrations were measured using ELISA. Background concentration (before injection) was 1.27 ± 0.27 ng/mL (mean ± SD). Including background concentration, the mean peak plasma concentration was obtained 15 min after injection (5.82 ± 3.75 ng/mL), and ranged from 3.79 to 2.20 ng/mL (30 min–3 h), remaining between 1.93 and 1.77 ng/mL (4–12 h), and declined to 1.40 ± 0.62 ng/mL at 24 h. Elimination half-life was 58.8 ± 40.2 min and clearance 56.7 ± 21.5 mL/min. Results indicate early rapid systemic uptake of buprenorphine from epidural administration with plasma concentrations similar to using buccal or IM routes by 15 min postinjection.     

Pharmacodynamics of amoxicillin against Mannheimia haemolytica and Pasteurella multocida and pharmacokinetic/pharmacodynamic (PK/PD) correlation in sheep

Silicone-made tissue cages were implanted in sheep. Blood serum (SBS) and tissue cage fluid (TCF) samples were collected after amoxicillin intravenous and intramuscular administrations, at the dose of 15 mg/kg. Amoxicillin pharmacodynamics were studied in an artificial culture medium, SBS and TCF with use of a Mannheimia haemolytica and a Pasteurella multocida strain. A concentration-independent antimicrobial activity of amoxicillin was confirmed for levels higher than 0.79–1.75 × MIC. This result favored the use of the percentage of the 24 h dosing interval during which drug levels remain above MIC as the appropriate pharmacokinetic/pharmacodynamic index. The subsequent correlation revealed that intravenous administration could be considered effective against “deep” infections caused by bacteria with MICs < 1 μg/mL or “shallow” infections caused by bacteria with MICs < 0.1 μg/mL. Intramuscular administration could be safely considered effective against both “deep” and “shallow” infections when the MICs of the targeted pathogens are lower than 1 μg/mL.     

Resveratrol decreases oxidative burst capacity and alters stimulated leukocyte cytokine production in vitro

IntroductionResveratrol, a naturally-occurring phytophenol, has been shown to bolster immune surveillance and reverse immunosenescence in a dose dependent manner in rodents and humans. Although safety and pharmacokinetic studies have been completed in dogs, the immunomodulatory effects of resveratrol in dogs has not yet been investigated. The objective of this study was to determine the effect of resveratrol on canine innate immune system function in vitro. The hypothesis was that similar to other species, low concentrations of resveratrol would stimulate while high concentrations would depress innate immune system function.MethodsWhole blood was collected from six healthy, adult, client-owned dogs and was incubated with resveratrol at final concentrations of 6000 ng ml⁻¹, 3000 ng ml⁻¹, 1000 ng ml⁻¹, or control solution for 4 h. Following incubation, phagocytosis and oxidative burst were evaluated using flow cytometry, and LPS-, lipoteichoic acid (LTA) – and peptidoglycan (PG)-stimulated leukocyte production of TNF, IL-6, and IL-10 were measured using a canine specific multiplex assay.ResultsPhagocytosis was not altered by resveratrol at any concentration compared to control. However, while the number of PMNs capable of performing oxidative burst did not change, the robustness of the reaction following stimulation with Escherichia coli and PMA was reduced in a dose dependent manner. In addition, LPS-, LTA-, PG, and PBS-stimulated TNF production was increased following incubation with all concentrations of resveratrol compared to control, and this effect was dose dependent. LTA-stimulated IL-6 was increased with resveratrol compared to control. Furthermore, LTA-stimulated IL-10 was decreased with 6000 ng ml⁻¹ and 3000 ng ml⁻¹ concentrations of resveratrol and PG-stimulated IL-10 production was decreased with all concentrations of resveratrol compared to control. The LPS-, LTA-, and PG-stimulated TNF:IL-10 ratio was increased with 6000 ng ml⁻¹ of resveratrol compared to control and lower resveratrol concentrations.ConclusionWhile resveratrol was sparing to PMN phagocytosis, it reduced the robustness of PMN oxidative burst. Resveratrol also increased pro-inflammatory and decreased anti-inflammatory leukocyte cytokine production capacity in vitro. These data suggest that resveratrol supplementation may depress oxidative burst reactions while promoting pro-inflammatory leukocyte cytokine production and decreasing anti-inflammatory cytokine production. Based on these findings, further in vivo study regarding the effects of resveratrol on PMN oxidative burst capability and leukocyte cytokine production capacity are indicated prior to routine supplementation.     

Pharmacokinetics of mequindox and its metabolites in rats after intravenous and oral administration

Pharmacokinetics of mequindox (MEQ) and its metabolites were determined in rats after intravenous (i.v.) and oral (p.o.) administration of MEQ at a single dose of 10 mg kg⁻¹ bodyweight. After both administrations, MEQ and five of its metabolites were quantified, except M4, whereas M1 and M2 were the predominant ones. The areas under the concentration–time curves (h ng mL⁻¹) of MEQ, M1, M2, M3, M5 and M10 after i.v. administration were 7559 ± 495, 6354 ± 2761, 5586 ± 2337, 1034 ± 160, 2370 ± 791 and 1813 ± 622, respectively, whereas after p.o. administration, remained as 2809 ± 40, 4361 ± 3544, 4351 ± 1046, 1444 ± 814, 3864 ± 305 and 1213 ± 569, respectively. The elimination half-lives (h) of these compounds after i.v. administration were 3.48 ± 0.80, 4.20 ± 0.76, 6.25 ± 2.41, 4.77 ± 1.54, 4.69 ± 1.62 and 16.89 ± 5.15, respectively, and were 3.21 ± 0.40, 3.66 ± 1.06, 4.20 ± 1.03, 8.91 ± 5.99, 4.20 ± 2.02 and 20.84 ± 10.85 after p.o. administration, respectively. After p.o. administration, the bioavailability of MEQ was 37.16%. The results showed that MEQ was extensively metabolized in rats and rapidly absorbed after p.o. administration.     

Anterior segment angiography of the normal canine eye: A comparison between indocyanine green and sodium fluorescein

The objective of this study was to assess and compare indocyanine green (IG) and sodium fluorescein (SF) angiographic findings in the normal canine anterior segment using a digital single lens reflex (dSLR) camera adaptor. Images were obtained from 10 brown-eyed Beagles, free of ocular and systemic disease. All animals received butorphanol (0.2 mg/kg IM), maropitant citrate (1.0 mg/kg SC) and diphenhydramine (2.0 mg/kg SC) 20 min prior to propofol (4 mg/kg IV bolus, 0.2 mg/kg/min continuous rate infusion). Standard color imaging was performed prior to the administration of 0.25% IG (1 mg/kg IV). Imaging was performed using a full spectrum dSLR camera, dSLR camera adaptor, camera lens (Canon 60 mm f/2.8 Macro) and an accessory flash. Images were obtained at a rate of 1/s immediately following IG bolus for 30 s, then at 1, 2, 3, 4 and 5 min. Ten minutes later, 10% SF (20 mg/kg IV) was administered. Imaging was repeated using the same adaptor system and imaging sequence protocol. Arterial, capillary and venous phases were identified during anterior segment IG angiography (ASIGA) and their time sequences were recorded.ASIGA offered improved visualization of the iris vasculature in heavily pigmented eyes compared to anterior segment SF angiography (ASSFA), since visualization of the vascular pattern during ASSFA was not possible due to pigment masking. Leakage of SF was noted in a total of six eyes. The use of IG and SF was not associated with any observed adverse events. The adaptor described here provides a cost-effective alternative to existing imaging systems.     

The dipeptidyl peptidase IV inhibitor NVP-DPP728 reduces plasma glucagon concentration in cats

Glucagon-like peptide-1 (GLP-1) analogues and inhibitors of its degrading enzyme, dipeptidyl peptidase IV (DPPIV), are interesting therapy options in human diabetics because they increase insulin secretion and reduce postprandial glucagon secretion. Given the similar pathophysiology of human type 2 and feline diabetes mellitus, this study investigated whether the DPPIV inhibitor NVP-DPP728 reduces plasma glucagon levels in cats. Intravenous glucose tolerance tests (ivGTT; 0.5 g/kg glucose after 12 h fasting) and a meal response test (test meal of 50% of average daily food intake, offered after 24 h fasting) were performed in healthy experimental cats. NVP-DPP728 (0.5–2.5 mg/kg IV or SC) significantly reduced glucagon output in all tests and increased insulin output in the ivGTT. Follow-up studies will investigate the potential usefulness as therapy in diabetic cats.     

Development of intraosseous infusion of the distal phalanx to access the foot lamellar circulation in the standing,conscious horse

Intraosseous (IO) infusion of the distal phalanx (IOIDP) as a delivery route targeting hoof lamellar tissue of standing, conscious horses was evaluated. Following sedation and regional nerve blockade in six Standardbred horses, a microdialysis (MD) probe was implanted into the hoof lamellar tissue of one forelimb. A purpose designed cannulated bone screw was introduced into the body of the distal phalanx, approximately 6 cm from the MD probe. Gentamicin solution (25 mg/mL) was infused at 20 μL/min through the bone screw for 2 h without the application of a tourniquet. MD and blood samples were collected at regular intervals and analysed for gentamicin concentrations.Gentamicin was present in lamellar tissue at much higher concentrations than peripheral serum. The mean concentration of gentamicin was 24.4, 20.5 and 4.4 μg/mL in extracellular fluid (ECF) and 0.28, 0.5 and 0.32 μg/mL in serum samples collected 60, 120 and 150 min after IOIDP was started, respectively. A clinically safe and efficacious IO drug delivery to the hoof lamellar tissue of standing, conscious horse was developed.     

PHARMACOKINETICS OF SINGLE-DOSE BUPRENORPHINE,BUTORPHANOL, AND HYDROMORPHONE IN THE DOMESTIC FERRET (MUSTELA PUTORIUS FURO)

The objective of this study was to establish the clinical pharmacokinetic profile of 4 different opioid drugs (buprenorphine, butorphanol, hydromorphone, and morphine) in the domestic ferret (Mustela putorius furo). Twenty-four, approximately 1-year-old, male neutered purpose-bred domestic ferrets were used for this study. The ferrets were divided into 4 groups of 6, with a different opioid drug used for each group. A preopioid venous blood sample was obtained via cranial vena cava venipuncture. Following the initial blood collection, a single injection of opioid (hydromorphone 0.1 mg/kg, buprenorphine 0.04 mg/kg, butorphanol 0.3 mg/kg, and morphine 1 mg/kg) was given to each ferret, dependent on assigned drug group, intramuscularly (buprenorphine) or subcutaneously (hydromorphone, butorphanol, and morphine). Intramuscular injections were administered in the semimembranosis and semitendinosis muscles, whereas the subcutaneous injections were delivered in the intrascapular subcutaneous space. A venous blood sample was obtained at 5, 15, 30, 60, 120, 240, 360, 480, and 720 minutes postinjection from the ferrets in the buprenorphine, butorphanol, and hydromorphone groups. Mass spectrometry and liquid chromatography was performed to obtain plasma concentrations of the administered drugs. The mean maximum concentration of buprenorphine was 6.96 ng/mL, butorphanol was 48.6 ng/mL, and hydromorphone was 17.3 ng/mL. Maximum concentrations were achieved at a mean of 9 minutes after administration for buprenorphine, 13.3 minutes for butorphanol, and 8.33 minutes for hydromorphone. The mean half-life of buprenorphine was 219.1 minutes, butorphanol was 91.1 minutes, and hydromorphone was 24.7 minutes. Owing to severe complications arising within the morphine group, including hypersalivation and vomiting, the morphine study was discontinued prior to blood sample collection. Intramuscular injections of buprenorphine and subcutaneous injections of butorphanol or hydromorphone appeared to be well tolerated by all ferrets. The pharmacokinetics of buprenorphine, butorphanol, and hydromorphone of a single equipotent dose of each drug have been established through this research investigation and may be useful for further studies.     

Nerve Stimulator–Guided Sciatic-Femoral Block in Pet Rabbits (Oryctolagus cuniculus) Undergoing Hind Limb Surgery: A Case Series

This article describes the clinical applicability of a nerve stimulator–guided technique, previously described in dogs, to block the sciatic and the femoral nerves in 4 pet rabbits (Oryctolagus cuniculus) undergoing hind limb surgeries. Preanesthetic intramuscular doses of medetomidine (0.08 mg/kg), ketamine (15 mg/kg), and buprenorphine (0.03 mg/kg) were administered to the rabbit patients. The rabbits were intubated and general anesthesia was maintained using isoflurane in oxygen. The sciatic-femoral nerve block was performed with 2% lidocaine at a volume of 0.05 mL/kg/nerve. Sciatic-femoral block was feasible in rabbits, and the motoric responses following electrical stimulation of both nerves were consistent with those reported in dogs after successful nerve location. Iatrogenic complications, namely nerve damage and local anesthetic toxicity, did not occur. Based on these results, the authors conclude that the sciatic-femoral nerve block described in dogs can be safely performed in rabbits. Clinical trials are required to assess the analgesic efficacy of the combined sciatic-femoral nerve block in rabbits as a part of multimodal pain management.     

Pharmacokinetics and efficacy of intravenous and extradural tramadol in dogs

Tramadol is a synthetic opioid agonist used extensively in human and, to a lesser extent, veterinary medicine throughout the world. The clinical efficacy and pharmacokinetic profile of intravenous (IV) and extradural (ED) tramadol (2 mg/kg) and its o-desmethyl metabolite were studied in dogs undergoing tibial plateau levelling osteotomy (TPLO). Intra-operative cardiorespiratory variables were monitored and post-operative pain was assessed using the short form of the Glasgow Composite Pain Scale. A rapid (<5 min) and effective production of o-desmethyl tramadol was recorded. The pharmacokinetic profile was similar for tramadol and its metabolite irrespective of the route of administration. ED tramadol provided sufficient intra- and post-operative analgesia without significant clinical side-effects, but the post-operative analgesia was comparable to that following IV administration and the ED route could therefore not be considered a practical alternative to the IV route.     

Assessment of the diagnostic accuracy of circulating natriuretic peptide concentrations to distinguish between cats with cardiac and non-cardiac causes of respiratory distress

ObjectivesTo determine if serum natriuretic peptide (NP) concentrations could distinguish cardiac from non-cardiac causes of respiratory distress (RD) in cats.AnimalsSeventy-four cats from 1 university hospital were used.MethodsSerum NP concentrations were measured in 41 cats with non-cardiac respiratory distress (RD-NC) and compared to 33 cats with RD due to congestive heart failure (RD + CHF) using sandwich enzyme immunoassays (ELISA).ResultsRD-NC cats had lower (P = 0.0001) median NT-proANP and NT-proBNP concentrations (614 and 45 fmol/mL, respectively) than RD + CHF cats (1690 and 523 fmol/mL, respectively). The area under the curve was 0.88 and 0.96 for the receiver operating curve analysis of the diagnostic accuracy of NT-proANP and NT-proBNP concentrations to discriminate RD + CHF from RD-NC cats (P = 0.036). An optimum cut-off concentration of 986 fmol/mL for NT-proANP and 220 fmol/mL for NT-proBNP accurately discriminated RD-NC from RC + CHF cats with a sensitivity of 93.8% and 93.9% and a specificity of 80.3% and 87.8%, respectively.ConclusionsSerum NP concentrations were different in RD + CHF cats compared to RD-NC cats. Evaluation of circulating NP concentrations may be helpful in the initial approach to cats presenting with respiratory distress, particularly if advances in ELISA technology result in a rapid cage-side test.     

Comparative pharmacokinetics of an injectable cephalexin suspension in beef cattle

This study describes and compares the pharmacokinetics of a single 7.5 mg/kg dose of cephalexin monohydrate oil-based 20% suspension after its administrations to six cows by the intramuscular (i.m.) and subcutaneous (s.c.) routes, and to five calves by the i.m. route. Significantly (P < 0.05) higher peak plasma concentrations (5.6 ± 0.79 μg/ml versus 3.93 ± 1.24 μg/ml) and lower half-life (1.81 ± 0.56 h versus 4.21 ± 0.82 h) and mean residence time (4.12 ± 1.07 h versus 6.63 ± 0.85 h) were obtained after i.m. administration when compared to the s.c. administration to cows. No differences were found between pharmacokinetic parameters calculated for cows and calves. Cephalexin plasma concentrations remained above 0.5–0.75 μg/ml for 11–14 h and 8–9 h after the s.c. and i.m. administrations, respectively. Thus, route of administration may be an important issue to be considered when calculating dosage schedules for successful treatments and safe withdrawal times for veterinary medicines.     

Pharmacokinetics,plasma protein binding and bioavailability of moxifloxacin in Muscovy ducks after different routes of administration

In this study the disposition kinetics and plasma availability of moxifloxacin in Muscovy ducks after single intravenous (i.v.), intramuscular (i.m.) and oral (p.o.) administrations of 5 mg kg^?1 b.wt. were investigated. The concentrations of moxifloxacin in the plasma were measured using high-performance liquid chromatography (HPLC) with fluorescence detection on samples collected at frequent intervals after drug administration. Following intravenous injection, the decline in plasma drug concentration was bi-exponential with half-lives of (t_1/2α) 0.22 ± 0.10 h and (t_1/2β) 2.49 ± 0.26 h for distribution and elimination phases, respectively. The volume of distribution at steady-state (V_dss) was 1.02 ± 0.14 l kg^?1 and the total body clearance (Cl_tot) was 0.32 ± 0.11 l kg^?1 h^?1, respectively. After intramuscular and oral administration of moxifloxacin at the same dose the peak plasma concentrations (C_max) were 2.38 ± 0.43 and 2.11 ± 0.36 μg ml^?1 and were obtained at 1.47 ± 0.26 and 1.83 ± 0.16 h (T_max), respectively, the elimination half-lives (T_1/2el) were 3.14 ± 0.42 and 2.63 ± 0.44 h, respectively, and AUC_0–24 were 15.87 ± 2.35 and 14.52 ± 2.37 μg ml^?1 h^?1, respectively. The systemic bioavailabilities were 96.36 ± 11.54% and 86.79 ± 12.64%, respectively. In vitro plasma protein binding percent was 32%. We concluded that moxifloxacin might be clinically interesting alternative for the treatment of most sensitive bacterial infections in Muscovy ducks.     

Pharmacokinetics of oral gabapentin in greyhound dogs

The purpose of this study was to assess the pharmacokinetics of gabapentin in healthy greyhound dogs after single oral doses targeted at 10 and 20 mg/kg PO. Six healthy greyhounds were enrolled (3 males, 3 females). Blood was obtained at predetermined times for the measurement of gabapentin plasma concentrations by liquid chromatography/mass spectrometry. Pharmacokinetic parameters were determined with computer software.The actual mean (and range) doses administered were 10.2 (9.1–12.0) mg/kg and 20.5 (18.2–24) mg/kg for the 10 mg/kg and 20 mg/kg targeted dose groups. The mean C_MAX for the 10 and 20 mg/kg groups were 8.54 and 13.22 μg/mL at 1.3 and 1.5 h, and the terminal half-lives were 3.3 and 3.4 h, respectively. The relative bioavailability of the 10 mg/kg group was 1.13 compared to the 20 mg/kg group. Gabapentin was rapidly absorbed and eliminated in dogs, indicating that frequent dosing is needed to maintain minimum targeted plasma concentrations.     

Development of an intra-lamellar microdialysis method for laminitis investigations in horses

Microdialysis (MD) was used for continuous monitoring of the lamellar extracellular fluid (ECF) in six mature healthy Standardbred horses. MD probes were introduced into the lamellar tissue under local anaesthesia. Following intravenous injection of gentamicin (5 mg/kg), MD and serum samples were collected for 24 h and analysed using a sensitive ELISA test for gentamicin and fluorescence polarization immunoassay for urea concentrations. Calibration of probes was performed through in vivo urea recovery and in vitro gentamicin and urea recovery. Data obtained from different body compartments were compared statistically. The concentration of gentamicin was significantly higher in serum than lamellar ECF for the first 8 h (P < 0.05), but remained above the minimum inhibitory concentration (MIC) in the ECF for a further 4 h. The method will be useful to monitor changes in the lamellar ECF during laminitis and the local kinetics of drugs used therapeutically for this condition.