Pharmacokinetics of buprenorphine after intravenous administration of clinical doses to dogs

The purpose of this study was to evaluate plasma concentrations and pharmacokinetic parameters of buprenorphine in dogs following intravenous (IV) administration of clinical doses of the opioid. An IV bolus of 0.02 mg/kg buprenorphine was administered to six healthy Beagles and blood samples were collected through a jugular catheter before and at 1, 5, 10, 15, 20, 30 and 45 min, and 1, 2, 4, 6, 8 and 12 h after administration. Plasma buprenorphine concentrations, measured using a commercial radioimmunoassay (RIA), decreased following a three-exponential curve. The two distribution and the elimination half-lives were 2.9 ± 1.8 min, 16.5 ± 3.7 min, and 266.6 ± 82.0 min, respectively; the clearance was 329.6 ± 62.2 mL/min, and the steady state volume of distribution was 83.7 ± 26.5 L.The results demonstrated the feasibility of the RIA assay to analyse buprenorphine in dog plasma samples. Following IV administration buprenorphine showed a three-compartment kinetic profile, as has been described previously in humans, rabbits and cats. The relationship between plasma concentrations and dynamic effects in dogs remains to be established.     

Antinociceptive effects of epidural buprenorphine or medetomidine, or the combination, in conscious cats

The aim of this study was to compare the antinociceptive effects of epidural buprenorphine (EB), epidural medetomidine (EM) or epidural buprenorphine–medetomidine (EBM). Eight cats were studied. Thermal thresholds (TT) were measured by increasing the temperature of a probe placed on the thorax. Mechanical thresholds (MT) were measured through inflation of a modified blood pressure bladder to the cat's forelimb. After baseline measurements, EB (0.02 mg/kg), EM (0.01 mg/kg) or half of the doses of each drug (EBM) were administered. Data were analysed using anova ( P  < 0.05) and 95% confidence interval (CI). TT increased from 30 min to 1 h after EB and at 45 min after EM. MT increased from 45 min to 2 h after EB, from 15 min to 1 h after EM and at 30, 45 min and at 2 h after EBM. MT were significantly lower after EB than EM at 30 min. TT were above the upper 95%CI from 15 min to 24 h after EB, from 15 min to 4 h after EM and from 15 min to 8 h after EBM. MT were above the upper 95%CI from 15 min to 5 h, and at 8, 12 and 24 h after EB, from 15 min to 6 h after EM and from 15 min to 6 h and at 12 and 24 h after EBM. All treatments had similar onset. Overall, EB presented longer period of action than EBM and EM. The same magnitude of analgesia was achieved, but with fewer side effects when EBM was compared with EM.     

Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by anova (P<0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8+/-3 degrees C), 1-3 h after methadone (maximum 3.4+/-1.9 degrees C) and 45 min to 1 h (maximum 3.4+/-2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238+/-206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255+/-232 mmHg) and 45-60 min and 3-6 h (maximum 255+/-232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes.     

Pharmacokinetics of doxycycline in sheep after intravenous and oral administration

The pharmacokinetics of doxycycline were investigated in sheep after oral (PO) and intravenous (IV) administration. The IV data were best described using a 2- (n = 5) or 3- (n = 6) compartmental open model. Mean pharmacokinetic parameters obtained using a 2-compartmental model included a volume of distribution at steady-state (V_ss) of 1.759 ± 0.3149 L/kg, a total clearance (Cl) of 3.045 ± 0.5264 mL/kg/min and an elimination half-life (t_1/2β) of 7.027 ± 1.128 h. Comparative values obtained from the 3-compartmental mean values were: V_ss of 1.801 ± 0.3429 L/kg, a Cl of 2.634 ± 0.6376 mL/kg/min and a t_1/2β of 12.11 ± 2.060 h. Mean residence time (MRT_0−∞) was 11.18 ± 3.152 h. After PO administration, the data were best described by a 2-compartment open model. The pharmacokinetic parameter mean values were: maximum plasma concentration (C_max), 2.130 ± 0.950 μg/mL; time to reach C_max (t_max), 3.595 ± 3.348 h, and absorption half-life (t_1/2k01), 36.28 ± 14.57 h. Non-compartmental parameter values were: C_max, 2.182 ± 0.9117 μg/mL; t_max, 3.432 ± 3.307 h; F, 35.77 ± 10.20%, and mean absorption time (MAT_0–∞), 25.55 ± 15.27 h. These results suggest that PO administration of doxycycline could be useful as an antimicrobial drug in sheep.     

Pharmacokinetic and pharmacodynamic modelling of intravenous,intramuscular and subcutaneous buprenorphine in conscious cats

ObjectiveTo describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats.Study designRandomized, prospective, blinded, three period crossover experiment.AnimalsSix healthy adult cats weighing 4.1 ± 0.5 kg.MethodsBuprenorphine (0.02 mg kg^?1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24 hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p < 0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics.ResultsTT increased above baseline from 15 to 480 minutes and at 30 and 60 minutes after IV and IM administration, respectively (p < 0.05). Maximum increase in TT (mean ± SD) was 9.3 ± 4.9 °C at 60 minutes (IV), 4.6 ± 2.8 °C at 45 minutes (IM) and 1.9 ± 1.9 °C at 60 minutes (SC). TT was significantly higher at 15, 60, 120 and 180 minutes, and at 15, 30, 45, 60 and 120 minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t_1/2k_e0 = 47.4 minutes) and receptor binding (k_on = 0.011 mL ng^?1 minute^?1). Persistence of thermal antinociception was due to slow receptor dissociation (t_1/2k_off = 18.2 minutes).Conclusions and clinical relevanceIV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats.     

Pharmacokinetics after intravenous, intramuscular and subcutaneous administration of moxifloxacin in sheep

The disposition kinetics of moxifloxacin, a fluoroquinolone antibiotic, after intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration was determined in sheep at a single dose of 5 mg/kg. The concentration-time data were analysed by compartmental (after IV dose) and non-compartmental (after IV, IM and SC administration) pharmacokinetic methods. Plasma concentrations of moxifloxacin were determined by high performance liquid chromatography with fluorescence detection. Steady-state volume of distribution (V_ss) and clearance (Cl) of moxifloxacin after IV administration were 2.03 ± 0.36 L/kg and 0.39 ± 0.04 L/h kg, respectively. Following IM and SC administration, moxifloxacin achieved maximum plasma concentration of 1.66 ± 0.62 mg/L and 0.90 ± 0.19 mg/L at 2.25 ± 0.88 h and 3.25 ± 1.17 h, respectively. The absolute bioavailabilities after IM and SC routes were 96.12 ± 32.70% and 102.20 ± 23.76%, respectively. From these data (kinetic parameters and absence of adverse reactions) moxifloxacin may be a potentially useful antibiotic in sheep.     

Effects of inhibition of nitric oxide synthase on systemic arterial pressure and renal vascular resistance in cats

These studies were undertaken to examine the systemic and renal effects of the pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100 μg kg⁻¹ bodyweight min⁻¹ resulted in a marked increase (P<0·001) in mean arterial pressure from the control value of 116·7 ± 4·6 mmHg to 154·2 ± 6·8 mmHg and an increase (P<0·05) in renal vascular resistance from the control value of 3·69 ± 0·33 mmHg min ml⁻¹ to 6·83 ± 1·15 mmHg min ml⁻¹. The increase in renal vascular resistance was generalised, with comparable increments in preglomerular and postglomerular vascular resistance. Mean values for glomerular capillary pressure (61·1 ± 61·9 vs 1·9 ± 1·6 mmHg), calculated from the sum of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did not change in response to the infusion of nitro-L-arginine. However, there was a marked reduction in renal blood flow (29·4 ± 3·1 to 16·9 ± 2·3 ml min⁻¹, P<0·01) and glomerular filtration rate (5·22 ± 0·57 to 3·52 ± 0·45 ml min⁻¹, P<0·01). These results provide evidence that EDNO plays an important role in the basal regulation of systemic arterial blood pressure and renal haemodynamics in cats.     

Pharmacokinetic‐pharmacodynamic modelling of intravenous buprenorphine in conscious horses

ObjectiveDescribe the pharmacokinetics of buprenorphine and norbuprenorphine in horses and to relate the plasma buprenorphine concentration to the pharmacodynamic effects.Study designSingle phase non-blinded study.AnimalsSix dedicated research horses, aged 3–10 years and weighing 480–515 kg.MethodsThermal and mechanical nociceptive thresholds, heart and respiratory rates and locomotor activity were measured before and 15, 30, 45 &; 60 minutes and 2, 4, 6, 8, 12 &; 24 hours post-administration of 10 μg kg⁻¹ buprenorphine IV. Intestinal motility was measured 1, 6, 12 &; 24 hours after buprenorphine administration. Venous blood samples were obtained before administration of buprenorphine 10 μg kg⁻¹ IV and 1, 2, 4, 6, 10, 15, 30, 45 &; 60 minutes, and 2, 4, 6, 8, 12 &; 24 hours afterwards. Plasma buprenorphine and norbuprenorphine concentrations were measured using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) assay with solid-phase extraction. A non-compartmental method was used for analysis of the plasma concentration–time data and plasma buprenorphine concentrations were modelled against two dynamic effects (change in thermal threshold and mechanical threshold) using a simple Emax model.ResultsPlasma buprenorphine concentrations were detectable to 480 minutes in all horses and to 720 minutes in two out of six horses. Norbuprenorphine was not detected. Thermal thresholds increased from 15 minutes post-buprenorphine administration until the 8–12 hour time points. The increase in mechanical threshold ranged from 3.5 to 6.0 Newtons (median: 4.4 N); and was associated with plasma buprenorphine concentrations in the range 0.34–2.45 ng mL⁻¹.Conclusions and clinical relevanceThe suitability of the use of buprenorphine for peri-operative analgesia in the horse is supported by the present study.     

Comparison of the effect of hypertonic hydroxyethyl starch and mannitol on the intraocular pressure in healthy normotensive dogs and the effect of hypertonic hydroxyethyl starch on the intraocular pressure in dogs with primary glaucoma

PURPOSE: The purpose of this study was to determine if intravenous hypertonic hydroxyethyl starch (7.5%/6%) (HES) could decrease the intraocular pressure (IOP) in healthy normotensive dogs, and compare its effect with that of mannitol (20%) (experimental study). In addition, the potential IOP-lowering effect of hypertonic HES was evaluated in six dogs with primary glaucoma (clinical study). MATERIAL AND METHODS: Experimental study: eight male ophthalmoscopically and clinically healthy Beagles were included in this study. The IOP of each dog was measured by applanation tonometry in both eyes to obtain control values at 10:00, 10:15, 10:30, 10:45, 11:00 a.m., and then every hour until 6:00 p.m. prior to the first treatment (control period). Each dog received, with at least 2-week intervals and in a random order, an intravenous (IV) infusion of 4 mL/kg hypertonic HES (1.2 g/kg NaCl; 0.96 g/kg HES) and 4 mL/kg mannitol 20% (1 g/kg) over a period of 15 min starting at 10:00 a.m. IOP was measured oculus uterque (OU) at the same time intervals as in the control study. The differences in IOP between the treatment groups and the baseline IOP (before the start of infusion), between oculus sinister (OS) and oculus dexter (OD) and between the same time points of all groups were determined with a Student's t-test for paired samples (P = 0.05). Clinical study: six dogs with primary glaucoma (representing seven eyes) received an IV infusion of 4 mL/kg hypertonic HES over a period of 15 min. IOP was measured before and 15 and 30 min after starting the infusion. RESULTS: Experimental study: no significant difference between IOP of both eyes was found. A significant decrease in IOP from baseline value was recorded at 15, 30, 45, and 60 min after the start of mannitol infusion (mean amplitude in IOP decrease 3.21 mmHg; P < 0.05) and at 15 and 30 min in dogs treated with HES (mean amplitude in IOP decrease 2.43 mmHg; P < 0.05). At 120 and 180 min there was a significantly higher IOP (P < 0.05) in HES treatment group compared to the values of the control group. Clinical study: in 5/7 eyes diagnosed with primary glaucoma a maximum decrease in IOP of an average of 24% from the baseline value (IOP before start of the infusion) was observed (range of decrease 2-21 mmHg). In three of these five cases the maximum decrease was reached at 15 min and in two cases at 30 min. In one case an increase in IOP of 35% (+ 18 mmHg) was seen after 15 min and 26% (+ 13 mmHg) after 30 min. Case 4 showed an increase in IOP of 5% (+ 3 mmHg) after 15 min and a decrease of 6% (- 4 mmHg) after 30 min. CONCLUSIONS: Intravenous hypertonic HES is comparable to intravenous mannitol 20% in lowering the intraocular pressure in healthy normotensive dogs. But this effect lasted half an hour longer after mannitol. In 6/7 eyes with primary glaucoma, hypertonic HES decreased IOP.     

Ingestion of energy, protein and amino acids from pasture by grazing European wild boar (Sus scrofa L.) in a semi-extensive production system

The aim of the study was to determine the apparent consumption of dry matter (DM), gross energy (GE), crude protein (CP) and amino acids (AA) from pasture by European wild boar in a pastoral system. Two pasture-types were used, one consisting predominantly of Lolium perenne L. and the other predominantly of Plantago lanceolata L. The study was conducted in Spring and repeated in Summer. Twelve purebred European Wild Boar of 18.8 ± 0.8 kg (mean ± sem) with nose rings were randomly grouped into six pairs. Each day of the 19-day study, a pair of animals was placed into each of three areas of a pasture strip (1.4 × 6.3 m per area) from each pasture type from 8:30 h until 16:30 h, after which the animals entered a barn and had free access to a commercial diet for 45 min, with each pasture strip being grazed once. Pasture samples were taken on days 4 to 19 from each grazed area pre- and post-grazing and the DM content of these samples was used to calculate DM consumption of the animals. Additional pasture samples were collected and analysed for gross energy, crude protein and amino acids. The wild boar consumed (mean + SEM) 418 ± 72.2 and 210 ± 38.3 g of DM per day in the L. perenne paddock during Spring and Summer, respectively, and 550 ± 85.9 and 226 ± 44.8 g DM per day in the P. lanceolata paddock during Spring and Summer, respectively. The amount of DM, energy, crude protein and amino acids that the animals consumed varied markedly between days, but did not significantly differ in amount between the L. perenne and P. laceolata paddocks. However, the consumptions were significantly lower in Summer than in Spring. It is estimated that the wild boar would have satisfied somewhat less than 90 and 45% of their daily maintenance digestible energy requirements through consumption of pasture when grazing the L. perenne paddock in Spring and Summer, respectively.     

The thermal antinociceptive effects of a high-concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats

ObjectiveTo evaluate the thermal antinociceptive effects of a high-concentration formulation of buprenorphine alone or followed by hydromorphone in conscious cats.Study designRandomized, blinded, placebo-controlled crossover study design.AnimalsA total of six purpose-bred, adult female ovariohysterectomized Domestic Short Hair cats.MethodsCats were allocated into three treatments each consisting of two injections, subcutaneous then intravenous (IV) administration, 2 hours apart: treatment SS, two injections of 0.9% saline; treatment BS, buprenorphine (0.24 mg kg^–1, 1.8 mg mL^–1) and saline; and treatment BH, buprenorphine (0.24 mg kg^–1) and hydromorphone (0.1 mg kg^–1). Skin temperature (ST) and thermal threshold (TT) were recorded before (baseline) and for 24 hours following first injection. TT data were analyzed using mixed linear models and a Benjamini–Hochberg sequential adjustment procedure (p < 0.05).ResultsThere were no significant differences among treatments for baseline ST and TT values, treatment SS over time and between treatments BS and BH. Compared with baseline, TT was significantly increased at all time points in treatments BH and BS except at 2 hours in treatment BS. TT was significantly higher than SS at 3–18 hours and 4–12 hours for treatments BS and BH, respectively. Maximal increases in TT were 47.5 °C at 2 hours, 53.9 °C at 3 hours and 52.4 °C at 6 hours in treatments SS, BS and BH, respectively.Conclusions and clinical relevanceAdministration of IV hydromorphone following high-concentration buprenorphine provided no additional antinociception and decreased the duration of effect when compared with high-concentration buprenorphine alone. Alternative analgesics should be considered if additional analgesia is required after administration of high-concentration buprenorphine.     

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.     

The pharmacokinetics and analgesic effects of extended‐release buprenorphine administered subcutaneously in healthy dogs

Buprenorphine is a partial μ agonist opioid used for analgesia in dogs. An extended‐release formulation (ER‐buprenorphine) has been shown to provide effective analgesia for 72 hr in rats and mice. Six healthy mongrel dogs were enrolled in a randomized, blinded crossover design to describe and compare the pharmacokinetics and pharmacodynamics of ER‐buprenorphine administered subcutaneous at 0.2 mg/kg (ER‐B) and commercially available buprenorphine for injection intravenously at 0.02 mg/kg (IV‐B). After drug administration, serial blood samples were collected to measure plasma buprenorphine concentrations using liquid chromatography/mass spectrometry detection. Heart rate, respiratory rate, body temperature, sedation score, and thermal threshold latency were recorded throughout the study. Median (range) terminal half‐life, time to maximum concentration, and maximum plasma concentration of ER‐buprenorphine were 12.74 hr (10.43–18.84 hr), 8 hr (4–36 hr), and 5.00 ng/ml (4.29–10.98 ng/ml), respectively. Mild bradycardia, hypothermia, and inappetence were noted in both groups. Thermal threshold latency was significantly prolonged compared to baseline up to 12 hr and up to 72 hr in IV‐B and ER‐B, respectively. These results showed that ER‐buprenorphine administered at a dose of 0.2 mg/kg resulted in prolonged and sustained plasma concentrations and antinociceptive effects up to 72 hr after drug administration.     

Validation of betapropiolactone (BPL) as an inactivant for infectious bovine rhinotracheitis (IBR) virus

Infectious bovine rhinotracheitis (IBR) virus causes vulvovaginitis, abortion and respiratory disease in cows and heifers. Betapropiolactone (BPL) is a disinfectant, effective against bacteria, fungi and viruses. It is also used to prepare inactivated vaccines because it destroys the nucleic acid core of viruses but does not damage the capsid. For the validation of BPL when used as an inactivant, it is more important to assure the quality of inactivating agent and the validity of the inactivation process. In the present study, the inactivation kinetics of IBR virus was determined with different concentration of BPL (1:250, 1:500, 1:1000, 1:1500, 1:2000 and 1:2500) at 4 and 37 °C. The result indicated that the BPL at 4 °C was able to inactivate the IBR virus within 4, 5 and 12 h with the concentration of 1:250, 1:500 and 1:1000, respectively. BPL at 37 °C was able to inactivate virus within 30 min with the concentration of 1:250. BPL with the concentration of 1:500 and 1:1000 were able to inactivate the virus within 120 min at 37 °C. Based on the kinetic study seven formulations were prepared and a sero conversion study of IBR inactivated vaccine was carried out. Serological response in animals to different formulations did not differ significantly (P > 0.05).     

Responses to condensed tannins of flowering sulla (Hedysarum coronarium L.) grazed by dairy sheep: Part 1: Effects on feeding behaviour, intake, diet digestibility and performance

The concentration of condensed tannins (CT) in sulla (Hedysarum coronarium L.) is moderate and overall regarded as beneficial. However, the intake of this forage can reduce diet digestibility, particularly during flowering phase. An experiment was run to assess the effect of CT on feeding behaviour, intake, diet digestibility and performance of dairy sheep rotationally grazing sulla at flowering phase. Twenty-four late-lactating sheep were blocked in two homogeneous groups and submitted to the following treatments: i) twice daily drenching with 200 g/day of a 50% w/v water solution of an anti-tannic substance, polyethylene glycol, group PEG; ii) twice daily drenching with 200 g/day of water, group CON (Control group). All the sheep rotationally grazed as a flock two sulla plots from April to June (8 weeks in total). Sward height, herbage mass, botanical and chemical composition of the herbage were measured at the beginning and the end of each grazing period. The feeding behaviour (3 sheep per group) was continuously monitored for 24 h in 6 weeks using the IGER behaviour recorders. Herbage DM intake (DMI), dietary DM digestibility (DMD) and apparent CP digestibility (CPD) were estimated on 8 sheep per group by the n-alkane method. On average, PEG group had longer total grazing (503 ± 12 vs 460 ± 12 min, P < 0.05) and eating time (425 ± 13 vs 391 ± 13 min, P < 0.07) than CON group. Moreover PEG group showed shorter inter-meal intervals (41 ± 3 vs 52 ± 3, min, P < 0.05) and higher number of daily meals than CT-exposed group (24 ± 1 vs 19 ± 1 min, P < 0.01). The herbage DMI was not affected by the treatment whereas DMD (74.60 ± 3.48 vs 58.30 ± 3.01%), and CPD (60.14 ± 4.83 vs 38.21 ± 4.83%) were both increased by PEG administration (P < 0.05) confirming the negative effect of sulla CT on these variables. Milk yield tended to be higher in PEG than CON (1331 ± 45 vs 1205 ± 59 ml, P < 0.11). Milk protein content was similar between groups while milk fat content was higher in CON than PEG ewes (6.61 ± 0.15 vs 6.11 ± 0.15%, P < 0.05), being the reverse true for milk urea (46.04 ± 1.27 vs 53.04 ± 0.76%, P < 0.001). To conclude, this experiment shows that when sulla is grazed at flowering as monoculture, dietary CT can exert negative effects on DM and CP apparent digestibility, in this study partially counterbalanced by a better metabolic utilisation of the nutrients up-taken.     

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.     

PK-PD modeling of buprenorphine in cats: intravenous and oral transmucosal administration

The pharmacokinetics and thermal antinociceptive effects of buprenorphine after intravenous (i.v.) or oral transmucosal (OTM) administration were studied in six adult cats. Plasma buprenorphine concentrations were measured using radioimmunoassay in a crossover study after a dose of 20 microg/kg given by the i.v. or OTM route. Oral pH was measured. Blood for drug analyses was collected before, and at 1, 2, 4, 6, 10, 15, 30, and 60 min and at 2, 4, 6, 8, 12, and 24 h after treatment. Thermal thresholds were measured before treatment, then following treatment every 30 min to 6 h, every 1 hour to 12 h and at 24 hours postadministration. Plasma buprenorphine concentration effect relationships were analyzed using a log-linear effect model. Oral pH was 9 in each cat. Peak plasma buprenorphine concentration was lower and occurred later in the OTM group but median bioavailability was 116.3%. Thermal thresholds increased significantly between 30 and 360 min in both groups. Peak effect was at 90 min and there was no difference at any time between the two groups. There was distinct hysteresis between plasma drug concentration and effect in both groups. Overall, OTM administration of buprenorphine is as effective as i.v. treatment and offers a simple, noninvasive method of administration which produces thermal antinociception for up to 6 h in cats.     

Effects of acepromazine, butorphanol and buprenorphine on thermal and mechanical nociceptive thresholds in horses

Reasons for performing study: To investigate the antinociceptive effects of buprenorphine administered in combination with acepromazine in horses and to establish an effective dose for use in a clinical environment. Objectives: To evaluate the responses to thermal and mechanical stimulation following administration of 3 doses of buprenorphine compared to positive (butorphanol) and negative (glucose) controls. Methods: Observer blinded, randomised, crossover design using 6 Thoroughbred geldings (3–10 years, 500–560 kg). Thermal and mechanical nociceptive thresholds were measured 3 times at 15 min intervals. Horses then received acepromazine 0.05 mg/kg bwt with one of 5 treatments i.v.: 5% glucose (Glu), butorphanol 100 µg/kg bwt (But) buprenorphine 5 µg/kg bwt (Bup5), buprenorphine 7.5 µg/kg bwt (Bup7.5) and buprenorphine 10 µg/kg bwt (Bup10). Thresholds were measured 15, 30, 45, 60, 90, 120, 150, 180, 230 min, 4, 5, 6, 7, 8, 9, 10, 11, 12 and 24 h post treatment administration. The 95% confidence intervals for threshold temperature (ΔT) for each horse were calculated and an antinociceptive effect defined as ΔT, which was higher than the upper limit of the confidence interval. Duration of thermal antinociception was analysed using a within‐subjects ANOVA and peak mechanical thresholds with a general linear model with post hoc Tukey tests. Significance was set at P<0.05. Results: Mean (± s.d.) durations of thermal antinociception following treatment administration were: Glu 0.5 (1.1), But 2.9 (2.0), Bup5 7.4 (2.3), Bup7.5 7.8 (2.7) and Bup10 9.4 (1.1) h. B5, B7.5 and B10 were significantly different from Glu and But. No serious adverse effects occurred, although determination of mechanical thresholds was confounded by locomotor stimulation. Conclusions: Administration of acepromazine and all doses of buprenorphine produced antinociception to a thermal stimulus for significantly longer than acepromazine and either butorphanol or glucose. Potential relevance: This study suggests that buprenorphine has considerable potential as an analgesic in horses and should be examined further under clinical conditions and by investigation of the pharmacokinetic/pharmacodynamic profile.     

Effects of intermittent suckling on the performance and digestive efficiency of Iberian piglets weaned at 35 days of age

During two consecutive replicates Iberian sows (n = 20) were subjected either to a conventional lactation (C) or intermittent suckling (IS). Piglets in the C treatment had free access to the dam. Piglets on IS treatment were separated from the sow during 6 h on days 29 and 30, 8 h on days 31 and 32, and 10 h on days 33 and 34. Litters on both treatments were weaned at 35 days of age and offered a starter diet until day 60 of age. The apparent digestibility (ApD) of nutrients and gross energy (GE) of the post-weaning diet was measured using Cr₂O₃ as external indigestible marker. Litters on IS tended to increase solid feed intake during the milk restriction (125 ± 12 vs. 70 ± 19 g piglet^− 1 day^− 1; P = 0.08). Feed intake was improved by IS during the second week post-weaning (676 ± 17 vs. 497 ± 12 g piglet^− 1 day^− 1, P < 0.01), but differences were totally offset after the 7th week of age. Differences in average growth rate of litters on C and IS treatments did not attain statistical significance during the period of restriction and in the first week post-weaning. Litters on IS showed increased growth rate during the second week post-weaning (422 ± 31 vs. 289 ± 33 g piglet^− 1 day^− 1; P = 0.01), but slower daily gains from the 3rd week post-weaning to 60 day of age than litters on C treatment (371 ± 14 vs. 432 ± 15 g piglet^− 1 day^− 1; P < 0.05). Nevertheless, neither at weaning nor at 60 days of age average body weight of piglets differed between treatments (7.71 ± 0.31 vs. 7.94 ± 0.30 kg for C and IS, at 35 days of age, 15.62 ± 0.65 vs. 16.20 ± 0.62 kg, at day 60). The apparent digestibility of nutrients of the starter diet offered after weaning remained unaffected by the treatment, except for a trend for higher ApD of GE for the piglets on IS treatment (P = 0.08). ApD for CP and GE was 78.1 ± 0.6 and 78.8 ± 0.3%, respectively. No significant differences in the proportions of total viscera and gastrointestinal tract to empty body weight (EBW) were observed between C and IS piglets at weaning and 60 d of age. In conclusion, the increase in feed intake observed prior and early after weaning as a consequence of intermittent suckling during the last week of 35 d lactation had no effect on nutrient digestibility measured at two weeks after weaning and failed on improving Iberian piglet performance.     

Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs during induction of anaesthesia with propofol

The cerebral state index (CSI) is used for monitoring EEG and depth of anaesthesia. The objective of this study was to analyse the correlation between ocular reflexes, CSI and estimated propofol plasma concentrations (PropCP) in dogs during induction of anaesthesia with propofol.Fourteen dogs were premedicated with acepromazine 0.05 mg kg⁻¹ IM. Anaesthesia was induced with a 200 ml h⁻¹ propofol 1% constant infusion rate until loss of corneal reflex using RugLoop II software with Beths’ pharmacokinetic model to estimate PropCp.Palpebral reflex (PR) and the corneal reflex (CR) were tested every 30 s and classified as present (+) or absent (−), and eyeball position was registered as rotated ventromedialy (ERV) or centred (EC).Heart rate (HR), mean arterial pressure (MAP) and CSI values were analyzed from baseline before the beginning of propofol infusion (T0) until loss of CR; CSI and PropCp, CSI and anaesthetic planes, and PropCp and anaesthetic planes were compared using correlation analysis.PropCp reached 7.65 ± 2.1 μg ml⁻¹ at the end of the study. CSI values at T0 were 89.2 ± 3.8. Based on the observation of ocular reflexes and eyeball position, it was possible to define five anaesthetic planes: A (superficial) to E (deep), being A (PR+/CR+/EC), B (PR+/ERV/CR+), C (PR−/ERV/CR+), D (PR−/EC/CR+) and E (PR−/EC/CR−). There was a significant correlation between PropCp and the anaesthetic planes (R = 0,861; P < 0.01). No significant correlation was observed between CSI and the anaesthetic planes or between CSI and PropCp. MAP decreased significantly from T0 until loss of corneal reflex (from 98 ± 14 mmHg to 82 ± 12 mmHg); HR did not change significantly (from 101 ± 30 bpm to 113 ± 16 bpm).The CSI monitoring was not consistent with the clinical observations observed in the different stages of depth anaesthesia. This could limit the use of CSI for monitoring depth of anaesthesia with propofol.