首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 46 毫秒
1.
ObjectiveTo investigate the pharmacokinetics of carprofen after a single intravenous (IV) dose and multiple oral doses administered to pigs undergoing electroporation of the pancreas.Study designProspective experimental study.AnimalsA group of eight female pigs weighing 31.74 ± 2.24 kg (mean ± standard deviation).MethodsCarprofen 4 mg kg?1 was administered IV after placement of a central venous catheter during general anaesthesia with isoflurane. Blood samples were collected 30 seconds before and 5, 10, 20, 30 and 60 minutes and 2, 4, 6, 8, 12 and 24 hours after carprofen administration. Subsequently, the same dose of carprofen was administered orally, daily, for 6 consecutive days and blood collected at 36, 48, 60, 72, 96, 120, 144 and 168 hours after initial carprofen administration. Plasma was analysed using liquid chromatography with mass spectrometry. Standard pharmacokinetic parameters were calculated by compartmental analysis of plasma concentration–time curves. Data are presented as mean ± standard error.ResultsThe initial plasma concentration of IV carprofen was estimated at 54.57 ± 3.92 μg mL?1 and decreased to 8.26 ± 1.07 μg mL?1 24 hours later. The plasma elimination curve showed a bi-exponential decline: a rapid distribution phase with a distribution half-life of 0.21 ± 0.03 hours and a slower elimination phase with an elimination half-life of 17.31 ± 3.78 hours. The calculated pharmacokinetic parameters were as follows: the area under the plasma concentration–time curve was 357.3 ± 16.73 μg mL?1 hour, volume of distribution was 0.28 ± 0.07 L kg?1 and plasma clearance rate was 0.19 ± 0.009 mL minute?1 kg?1. The plasma concentration of carprofen, administered orally from days 2 to 7, varied from 9.03 ± 1.87 to 11.49 ± 2.15 μg mL?1.Conclusions and clinical relevanceCarprofen can be regarded as a long-acting non-steroidal anti-inflammatory drug in pigs.  相似文献   

2.
Lidocaine has been reported to decrease the minimum alveolar concentration (MAC) of inhalation anesthetics in several species and has been used clinically to reduce the requirements for other anesthetic drugs. This study examined the effects of intravenous lidocaine on isoflurane MAC in cats. Six cats were studied. In experiment 1, the MAC of isoflurane was determined. An intravenous bolus of lidocaine 2 mg kg–1 was then administrated and venous plasma lidocaine concentrations measured to determine pharmacokinetic values. In experiment 2, lidocaine was administered to achieve target plasma concentrations between 1 and 11 μg mL–1 and the MAC of isoflurane was determined in triplicate at each lidocaine plasma concentration, using the tail‐clamp method. End‐tidal isoflurane concentration was determined using a calibrated infrared analyzer. Systolic blood pressure (Doppler), SpO2 and end‐tidal PCO2 (calibrated Raman spectrometer) were measured prior to each MAC determination. Body temperature was maintained between 38.5 and 39.5 °C by supplying external heat as needed. MAC values at the different lidocaine plasma concentrations were analyzed by a repeated measures ANOVA , using the Huynh–Feldt correction. The MAC of isoflurane in these cats was 2.21 ± 0.17. For the target concentrations of 1, 3, 5, 7, 9, and 11 μg mL–1, the actual lidocaine plasma concentrations was 1.06 ± 0.12, 2.83 ±0.39, 4.93 ± 0.64, 6.86 ± 0.97, 8.86 ± 2.10, and 9.84 ± 1.34 μg mL–1, respectively. At these target concentrations, the MAC of isoflurane was 2.14 ± 0.14, 1.88 ± 0.18, 1.66 ± 0.16, 1.47 ±0.13, 1.33 ± 0.23, and 1.06 ± 0.19%, respectively. Lidocaine, at target plasma concentrations of 1, 3, 5, 7, 9, and 11 μg mL–1, linearly decreased isoflurane MAC by –6 to 6, 7 to 28, 19 to 35, 28 to 45, 29 to 53, and 44 to 59%, respectively. Lidocaine significantly dose‐dependently and linearly decreases the requirements for isoflurane in cats. No ceiling effect was observed within the range of plasma concentrations studied.  相似文献   

3.
ObjectiveTo describe the pharmacokinetics of pregabalin in normal dogs after a single oral dose.Study designProspective experiment.AnimalsSix adult Labrador/Greyhound dogs (four females and two males) aged 2.6 (2.6–5.6) years old (median and range) weighing 33.4 (26.8–42.1) kg.MethodsAfter jugular vein catheterization, the dogs received a single oral dose of pregabalin (～4 mg kg?1). Blood samples were collected at: 0 (before drug administration), 15 and 30 minutes and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24 and 36 hours after drug administration. Plasma pregabalin concentration was measured by HPLC. Noncompartmental analysis was used to estimate pharmacokinetic variables.ResultsNo adverse effects were observed. The median (range) pharmacokinetic parameters were: Area under the curve from time 0 to 36 hours = 81.8 (56.5–92.1) μg hour mL?1; absorption half-life = 0.38 (0.25–1.11) hours; elimination half-life = 6.90 (6.21–7.40) hours; time over 2.8 μg mL?1 (the presumed minimal effective concentration) = 11.11 (6.97–14.47) hours; maximal plasma concentration (Cmax) = 7.15 (4.6–7.9) μg mL?1; time for Cmax to occur = 1.5 (1.0–4.0) hours. Assuming an 8-hour dosing interval, predicted minimal, average, and maximal steady state plasma concentrations were 6.5 (4.8–8.1), 8.8 (7.3–10.9), and 13.0 (8.8–15.2) μg mL?1. The corresponding values assuming a 12-hour interval were 3.8 (2.4–4.8), 6.8 (4.9–7.9), and 10.1 (6.6–11.6) μg mL?1.Conclusions and clinical relevancePregabalin 4 mg kg?1 PO produces plasma concentrations within the extrapolated therapeutic range from humans for sufficient time to suggest that a twice daily dosing regime would be adequate. Further study of the drug's safety and efficacy for the treatment of neuropathic pain and seizures in dogs is warranted.  相似文献   

4.
Objective To characterize intravenous anaesthesia with detomidine, ketamine and guaiphenesin in pregnant ponies. Animals Twelve pony mares, at 260–320 days gestation undergoing abdominal surgery to implant fetal and maternal vascular catheters. Materials and methods Pre‐anaesthetic medication with intravenous (IV) acepromazine (30 µg kg?1), butorphanol (20 µg kg?1) and detomidine (10 µg kg?1) preceded induction of anaesthesia with detomidine (10 µg kg?1) and ketamine (2 mg kg?1) IV Maternal arterial blood pressure was measured directly throughout anaesthesia and arterial blood samples were taken at 20‐minute intervals for measurement of blood gases and plasma concentrations of cortisol, glucose and lactate. Anaesthesia was maintained with an IV infusion of detomidine (0.04 mg mL?1), ketamine (4 mg mL?1) and guaiphenesin (100 mg mL?1) (DKG) for 140 minutes. Oxygen was supplied by intermittent positive pressure ventilation (IPPV) adjusted to maintain PaCO2 between 5.0 and 6.0 kPa (38 and 45 mm Hg), while PaO2 was kept close to 20.0 kPa (150 mm Hg) by adding nitrous oxide. Simultaneous fetal and maternal blood samples were withdrawn at 90 minutes. Recovery quality was assessed. Results DKG was infused at 0.67 ± 0.17 mL kg?1 hour?1 for 1 hour then reduced, reaching 0.28 ± 0.14 mL kg?1 hour?1 at 140 minutes. Arterial blood gas values and pH remained within intended limits. During anaesthesia there was no change in heart rate, but arterial blood pressure decreased by 10%. Plasma glucose and lactate increased (10‐fold and 2‐fold, respectively) and cortisol decreased by 50% during anaesthesia. Fetal umbilical venous pH, PO2 and PCO2 were 7.34 ± 0.06, 5.8 ± 0.9 kPa (44 ± 7 mm Hg) and 6.7 ± 0.8 kPa (50 ± 6 mm Hg); and fetal arterial pH, PO2 and PCO2 were 7.29 ± 0.06, 4.0 ± 0.7 kPa (30 ± 5 mm Hg) and 7.8 ± 1.7 kPa (59 ± 13 mm Hg), respectively. Surgical conditions were good but four ponies required a single additional dose of ketamine. Ponies took 60 ± 28 minutes to stand and recovery was good. Conclusions and clinical relevance Anaesthesia produced with DKG was smooth while cardiovascular function in mare and fetus was well preserved. This indicates that DKG infusion is suitable for maintenance of anaesthesia in pregnant equidae.  相似文献   

5.

Objective

To determine plasma bupivacaine concentrations after retrobulbar or peribulbar injection of bupivacaine in cats.

Study design

Randomized, crossover, experimental trial with a 2 week washout period.

Animals

Six adult healthy cats, aged 1–2 years, weighing 4.6 ± 0.7 kg.

Methods

Cats were sedated by intramuscular injection of dexmedetomidine (36–56 μg kg?1) and were administered a retrobulbar injection of bupivacaine (0.75 mL, 0.5%; 3.75 mg) and iopamidol (0.25 mL), or a peribulbar injection of bupivacaine (1.5 mL, 0.5%; 7.5 mg), iopamidol (0.5 mL) and 0.9% saline (1 mL) via a dorsomedial approach. Blood (2 mL) was collected before and at 5, 10, 15, 22, 30, 45, 60, 120, 240 and 480 minutes after bupivacaine injection. Atipamezole was administered approximately 30 minutes after bupivacaine injection. Plasma bupivacaine and 3-hydroxybupivacaine concentrations were determined using liquid chromatography–mass spectrometry. Bupivacaine maximum plasma concentration (Cmax) and time to Cmax (Tmax) were determined from the data.

Results

The bupivacaine median (range) Cmax and Tmax were 1.4 (0.9–2.5) μg mL?1 and 17 (4–60) minutes, and 1.7 (1.0–2.4) μg mL?1, and 28 (8–49) minutes, for retrobulbar and peribulbar injections, respectively. In both treatments the 3-hydroxybupivacaine peak concentration was 0.05–0.21 μg mL?1.

Conclusions and clinical relevance

In healthy cats, at doses up to 2 mg kg?1, bupivacaine peak plasma concentrations were approximately half that reported to cause arrhythmias or convulsive electroencephalogram (EEG) activity in cats, and about one-sixth of that required to produce hypotension.  相似文献   

6.
Morphine is considered the prototypical opiate analgesic. Despite the common use of morphine in dogs, ideal dosing strategies have not been formulated due to the difficulty in assessing its analgesic effects. The purpose of this study was to: 1) evaluate a noninvasive mechanical threshold device (von Frey device) to measure antinociceptive responses (pharmacodynamics) of opiates in dogs and 2) evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous (IV) morphine in dogs. Six healthy Beagle dogs were used. The von Frey threshold (vFT) response was evaluated hourly for 8 hours in each dog to examine the effect of repeated testing (controls). PK and PD (vFT) measurements were then made following a 1 mg kg–1 IV bolus of morphine sulfate. A two way blinded crossover consisted of an 8 hour IV constant rate infusion of saline or morphine with hourly PD measurements. The individual CRI was based on individual PK data and adjusted every 2 hours to attain targeted plasma concentrations of morphine of 10, 20, 30, and 40 ng mL–1. Blood samples were taken hourly in all phases, except the controls. No significant (p > 0.05) intraindividual changes in vFT occurred in the controls over 8 hours. The morphine bolus produced increased vFT at 1, 2, 3, and 4 hours post injection (p < 0.05). The EMAX and EC50 following the IV bolus were 213 ± 104% (increase from baseline) and 13.9 ± 5.8 ng mL–1, respectively. The CRI produced increased vFT at plasma concentrations >30 ng mL–1, when compared to saline controls (p < 0.05). Targeted plasma concentrations were inconsistent at higher infusion rates, suggesting the PK of morphine may change during CRI. The actual mean ± SD CRI plasma concentrations (ng ml–1) were 10.8 ± 3.0, 22.7 ± 7.4, 32.4 ± 13.9, 35.7 ± 16.9. Morphine dosing protocols should be re‐evaluated, as sufficient analgesia may not be obtained from published dosages. Intravenous boluses may be more predictable than CRI.  相似文献   

7.
ObjectiveNon-steroidal anti-inflammatory drugs are inhibitors of cyclooxygenase (COX) in tissues and used as therapeutic agents in different species. Grapiprant, a member of the piprant class of compounds, antagonizes prostaglandin receptors. It is a highly selective EP4 prostaglandin E2 receptor inhibitor, thereby limiting the potential for adverse effects caused by wider COX inhibition. The objectives of this study were to determine if the approved canine dose would result in measurable concentrations in horses, and to validate a chromatographic method of analysis for grapiprant in urine and plasma.Study designExperimental study.AnimalsA total of six healthy, adult mixed-breed mares weighing 502 ± 66 (397–600) kg and aged 14.8 ± 5.3 (6–21) years.MethodsMares were administered one dose of 2 mg kg–1 grapiprant via nasogastric tube. Blood and urine samples were collected prior to and up to 48 hours after drug administration. Drug concentrations were measured using high-performance liquid chromatography.ResultsGrapiprant plasma concentrations ranged from 71 to 149 ng mL–1 with the mean peak concentration (106 ng mL–1) occurring at 30 minutes. Concentrations were below the lower limit of quantification (50 ng mL–1) in four of six horses at 1 hour and in all six horses by 2 hours after drug administration. Grapiprant urine concentrations ranged from 40 to 4077 ng mL–1 and were still detectable at 48 hours after administration.Conclusions and clinical relevanceCurrently, there are no published studies looking at the pharmacodynamics of grapiprant in horses. The effective concentration needed to control pain in dogs ranges 114–164 ng mL–1. Oral administration of grapiprant (2 mg kg–1) in horses did not achieve those concentrations. The dose was well tolerated; therefore, studies with larger doses could be conducted.  相似文献   

8.

Objective

To characterize the pharmacokinetics of dexmedetomidine, MK-467 and their combination following intramuscular (IM) administration to cats.

Study design

Prospective randomized crossover experimental study.

Animals

A total of eight healthy adult male castrated cats aged 1–2 years.

Methods

Cats were administered dexmedetomidine (25 μg kg–1) IM (treatment D25IM) or intravenously (IV; treatment D25IV); MK-467 (600 μg kg–1) IM (treatment MK600IM) or IV (treatment MK600IV); or dexmedetomidine (25 μg kg–1) IM with 300, 600 or 1200 μg kg–1 MK-467 IM (treatments D25MK300IM, D25MK600IM and D25MK1200IM). D25MK600IM was the only combination treatment analyzed. Blood samples were obtained prior to drug administration and at various times for 5 hours (D25IV) or 8 hours (all other treatments) thereafter. Plasma dexmedetomidine and MK-467 concentrations were measured using liquid chromatography/mass spectrometry. Compartment models were fitted to the time–concentration data.

Results

A one-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IM, and the time–plasma MK-467 concentration data in cats administered MK600IM and D25MK600IM. A two-compartment model best fitted the time–plasma dexmedetomidine concentration data in cats administered D25IV and D25MK600IM, and the time–plasma MK-467 concentration data in cats administered MK600IV. Median (range) area under the time–concentration curve, absorption rate half-life, maximum concentration, time to maximum concentration and terminal half-life for dexmedetomidine in D25IM and D25MK600IM were 1129 (792–1890) and 924 (596–1649) ng minute mL–1, 4.4 (0.4–15.7) and 2.3 (0.2–8.0) minutes, 10.2 (4.8–16.9) and 17.8 (15.8–73.5) ng mL–1, 17.8 (2.6–44.9) and 5.2 (1.2–15.1) minutes and 62 (52–139) and 50 (31–125) minutes, respectively. Rate of absorption but not systemic exposure was significantly influenced by treatment. No significant differences were observed in MK-467 pharmacokinetic parameters in MK600IM and D25MK600IM.

Conclusions and clinical relevance

MK-467 significantly influenced the disposition of dexmedetomidine, whereas dexmedetomidine did not significantly affect the disposition of MK-467 when the drugs were coadministered IM.  相似文献   

9.
MKM–OS anesthesia provides general anesthesia with minimum cardiovascular depression in experimental horses. The purpose of this study was to evaluate the effect of MKM–OS anesthesia in clinical cases. Sixty‐eight horses were anesthetized with MKM–OS anesthesia for selective or emergency surgery. The horse physical status was categorized based upon the American Society of Anesthesiologists (ASA) classification scheme. Forty‐four horses were classified as ASA I or II (low‐risk; 30 soft tissue, eight ophthalmic, and six orthopedic surgeries) and 24 horses were classified as ASA III to V (high‐risk; 24 emergency colic surgeries). All horses were administered medetomidine (0.005 mg kg–1 IV) as premedication and anesthetized with ketamine (2.5 mg kg–1 IV) and midazolam (0.04 mg kg–1 IV). The horses were orotracheally intubated and connected to a large animal breathing circuit that delivered oxygen‐sevoflurane and administered the midazolam (0.8 mg mL–1)‐ketamine (40 mg mL–1)‐medetomidine (0.05 mg mL–1) drug combination at a rate of 0.025 mL kg–1 hour–1. Surgical anesthesia was maintained by controlling the dial setting of the sevoflurane vaporizer and achieved by delivering 1.6–1.8% of end‐tidal sevoflurane concentration. All horses were mechanically ventilated during anesthesia. Hypercapnia and hypoxia were not sufficiently improved in high‐risk horses (PaCO2; low‐risk 45–53 mm Hg versus high‐risk 56–60 mm Hg, p < 0.01: PaO2 low‐risk 248–388 mm Hg versus high‐risk 95–180 mm Hg, p < 0.01). Heart rate was significantly higher in high‐risk horses (low‐risk 37–42 bpm versus high‐risk 44–73 bpm, p < 0.01). Dobutamine infusion was required in five low‐risk (11%) and 17 high‐risk horses (68%) to maintain mean arterial blood pressure >70 mm Hg. Eleven high‐risk horses died during the perioperative period (three euthanized during surgery, two died during recovery, six died after recovery). The quality of recovery was good in low‐risk horses and good to satisfactory in high‐risk horses. MKM–OS anesthesia provided excellent surgical anesthesia with minimal to mild cardiovascular depression in low risk‐horses and mild to moderate cardiovascular depression in high risk‐horses. The possibility of preserve cardiovascular function could be the advantage of MKM–OS anesthesia in high‐risk horses.  相似文献   

10.
ObjectiveTo investigate the pharmacokinetics of orally and intravenously (IV) administered meloxicam in semi-domesticated reindeer (Rangifer tarandus tarandus).Study designA crossover design with an 11 day washout period.AnimalsA total of eight young male reindeer, aged 1.5–2.5 years and weighing 74.3 ± 6.3 kg, mean ± standard deviation.MethodsThe reindeer were administered meloxicam (0.5 mg kg–1 IV or orally). Blood samples were repeatedly collected from the jugular vein for up to 72 hours post administration. Plasma samples were analysed for meloxicam concentrations with ultraperformance liquid chromatography combined with triple quadrupole mass spectrometry. Noncompartmental analysis for determination of pharmacokinetic variables was performed.ResultsThe pharmacokinetic values, median (range), were determined. Elimination half-life (t½) with the IV route (n = 4) was 15.2 (13.2–16.8) hours, the volume of distribution at steady state was 133 (113–151) mL kg?1 and clearance was 3.98 (2.63–5.29) mL hour–1 kg–1. After oral administration (n = 7), the peak plasma concentration (Cmax) was detected at 6 hours, t½ was 19.3 (16.7–20.5) hours, Cmax 1.82 (1.17–2.78) μg mL–1 and bioavailability (n = 3) 49 (46–73)%. No evident adverse effects were detected after either administration route.Conclusions and clinical relevanceA single dose of meloxicam (0.5 mg kg–1 IV or orally) has the potential to maintain the therapeutic concentration determined in other species for up to 3 days in reindeer plasma.  相似文献   

11.
ObjectiveTo evaluate the pharmacokinetics of amitriptyline and its active metabolite nortriptyline after intravenous (IV) and oral amitriptyline administration in healthy dogs.Study designProspective randomized experiment.AnimalsFive healthy Greyhound dogs (three males and two females) aged 2–4 years and weighing 32.5–39.7 kg.MethodsAfter jugular vein catheterization, dogs were administered a single oral or IV dose of amitriptyline (4 mg kg−1). Blood samples were collected at predetermined time points from baseline (0 hours) to 32 hours after administration and plasma concentrations of amitriptyline and nortriptyline were measured by liquid chromatography triple quadrupole mass spectrometry. Non-compartmental pharmacokinetic analyses were performed.ResultsOrally administered amitriptyline was well tolerated, but adverse effects were noted after IV administration. The mean maximum plasma concentration (CMAX) of amitriptyline was 27.4 ng mL−1 at 1 hour and its mean terminal half-life was 4.33 hours following oral amitriptyline. Bioavailability of oral amitriptyline was 6%. The mean CMAX of nortriptyline was 14.4 ng mL−1 at 2.05 hours and its mean terminal half-life was 6.20 hours following oral amitriptyline.Conclusions and clinical relevanceAmitriptyline at 4 mg kg−1 administered orally produced low amitriptyline and nortriptyline plasma concentrations. This brings into question whether the currently recommended oral dose of amitriptyline (1–4 mg kg−1) is appropriate in dogs.  相似文献   

12.
Little is known about the analgesic action of buprenorphine (BUP) in cats. Relative to man, the cat has a more alkaline oral pH, which may make this an effective route for administering BUP in this species. This study aimed to assess and compare the pharmacokinetics and pharmacodynamics of sublingual (S‐L) and IV administration of BUP. Thermal threshold (TT) was measured and blood samples were collected following IV or S‐L administration (20 µg kg?1) of the injectable formulation. Six cats (five spayed females, one castrated male, 4.1–6.6 kg) were used. Each cat received both treatments in a randomized cross‐over study design with 1 month between experiments. Twenty‐four hours prior to each study, the lateral thorax of each of the cats was shaved, cephalic and jugular catheters placed, and oral pH measured. On the day of the study, TT was measured using a ‘thorax‐mounted’ thermal threshold‐testing device specifically developed for cats. The cats were free to move around. Skin temperature was recorded before each test, then the heater activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. The thermal threshold cut‐off point was 55.5 °C. Three baseline thresholds were recorded before treatment with S‐L or IV (via cephalic catheter) BUP (20 µg kg?1). Blood was withdrawn (jugular) at 1, 2, 4, 6, 10, 15, 30, 45, 60 minutes and at 2, 4, 6, 8, 12, and 24 hours post‐administration. TT was measured every 30 minutes?6 hours, 1–12 hours, and at 24 hours post‐administration. Plasma was immediately separated, stored at ?20.5 °C, and assayed within 4 months using a commercially available 125I radioimmunoassay. Threshold data were analyzed using anova with a repeat factor of time. No adverse effects were noted. Pupils were dilated for up to 9 hours post‐BUP. Behavioral changes were calm euphoria. Measured oral pH was 9 in each cat. Pre‐treatment mean threshold (±SD) was 41.2 ± 0.9 °C in the S‐L group and 40.8 ± 0.85 °C in the IV group. There were no significant differences between the groups with respect to thresholds over time (p = 0.72). Thresholds were significantly increased from 30 to 360 minutes in both the groups (>44.615 °C). Peak plasma BUP (Cmax) was lower (11 ± 6.7 ng mL?1vs. 92.9 ± 107.9 ng mL?1) and occurred later (Tmax) (30 minutes vs. 1 minute) after S‐L compared to IV administration, respectively. BUP (20 µg kg?1)‐administered S‐L or IV provided antinociception between 30 and 360 minutes after administration. Plasma levels did not correspond to TT.  相似文献   

13.
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.  相似文献   

14.
Objective To evaluate disposition of a single dose of butorphanol in goats after intravenous (IV) and intramuscular (IM) administration and to relate behavioral changes after butorphanol administration with plasma concentrations. Design Randomized experimental study. Animals Six healthy 3‐year‐old neutered goats (one male and five female) weighing 46.5 ± 10.5 kg (mean ± D). Methods Goats were given IV and IM butorphanol (0.1 mg kg?1) using a randomized cross‐over design with a 1‐week interval between treatments. Heparinized blood samples were collected at fixed intervals for subsequent determination of plasma butorphanol concentrations using an enzyme linked immunosorbent assay (ELISA). Pharmacokinetic values (volume of distribution at steady state [VdSS], systemic clearance [ClTB], extrapolated peak plasma concentration [C0] or estimated peak plasma concentration [CMAX], time to estimated peak plasma concentration [TMAX], distribution and elimination half‐lives [t1/2], and bioavailability) were calculated. Behavior was subjectively scored. A two‐tailed paired t‐test was used to compare the elimination half‐lives after IV and IM administration. Behavioral scores are reported as median (range). A Friedman Rank Sums test adjusted for ties was used to analyze the behavioral scores. A logit model was used to determine the effect of time and concentration on behavior. A value of p < 0.05 was considered significant. Results Volume of distribution at steady state after IV administration of butorphanol was 1.27 ± 0.73 L kg?1, and ClTB was 0.0096 ± 0.0024 L kg?1 minute?1. Extrapolated C0 of butorphanol after IV administration was 146.5 ± 49.8 ng mL?1. Estimated CMAX after IM administration of butorphanol was 54.98 ± 14.60 ng mL?1, and TMAX was 16.2 ± 5.2 minutes; bioavailability was 82 ± 41%. Elimination half‐life of butorphanol was 1.87 ± 1.49 and 2.75 ± 1.93 hours for IV and IM administration, respectively. Goats became hyperactive after butorphanol administration within the first 5 minutes after administration. Behavioral scores for goats were significantly different from baseline at 15 minutes after IV administration and at 15 and 30 minutes after IM administration. Both time and plasma butorphanol concentration were predictors of behavior. Behavioral scores of all goats had returned to baseline by 120 minutes after IV administration and by 240 minutes after IM administration. Conclusions and Clinical Relevance The dose of butorphanol (0.1 mg kg?1, IV or IM) being used clinically to treat postoperative pain in goats has an elimination half‐life of 1.87 and 2.75 hours, respectively. Nonpainful goats become transiently excited after IV and IM administration of butorphanol. Clinical trials to validate the efficacy of butorphanol as an analgesic in goats are needed.  相似文献   

15.
Newer techniques for cardiac output (Q) determinations that are minimally invasive remain to be validated in neonatal foals against other accepted techniques such as the lithium technique (LiDCO). This study compares Q determinations using the partial CO2 rebreathing technique (NICO) with LiDCO in anesthetized neonatal foals. Ten foals were instrumented for NICO and LiDCO determinations. For each foal low, intermediate and high levels of cardiac output were achieved in that order using an end‐tidal isoflurane (ETI) concentration of 1.3 – 2.1% for the lowest rate; an ETI of 0.85–1.4% and a constant‐rate infusion of dobutamine (1–3 ?g/kg/min) for the intermediate rate; and an ETI of 0.83–1% and dobutamine (2–6 ?g/kg/min) for the highest rate. Four foals also received IV intermittent doses (total cumulative dose of 1.1–1.7 mg) of phenylephrine at the highest rate of Q. The measurements were obtained in duplicate or triplicate for each Q technique after achieving a stable hemodynamic plane for at least 15 minutes at each rate of Q. For the lithium technique, all foals received 1.1–1.9 mL (0.16–0.28 mmol) of lithium. A Bland‐Altman analysis was used to compare the bias and precision of the two techniques. Eighty seven comparisons were determined between the two techniques. Eight were excluded due to more than 20% variation between the LiDCO determinations or technical errors at the time of determination. The correlation coefficient between the two methods was 0.67 for all Q determinations. Mean LiDCO and NICO values from 79 measurements were 130 ± 40 mL–1 kg minute–1 (range, 68– 237) and 152 ± 31 mL–1 kg minute–1 (89 – 209), respectively. The mean ( mL–1 kg minute–1) of the differences of LiDCO – NICO was = –0.7248 + 0.8602 NICO. The precision (1.96 SD) of the differences between LiDCO and NICO was 58.9 mL–1 kg minute–1 (–80.9–+36.9) with a mean difference of –22 mL–1 kg minute–1 (bias; 95% CI – 15.2 to ‐28.7). In conclusion, given the small bias compared to the limits of agreement, the NICO technique for determining Q deserves further consideration for adoption into clinical practice in neonatal foals.  相似文献   

16.
Objective To compare plasma colloid osmotic pressure (COP) of both maternal and fetal blood, before and after hemorrhage, and replenishment with Oxyglobin Solution (Biopure Corporation, Cambridge, MA, USA), hetastarch or whole blood in pregnant ewes. Study design Prospective, randomized study. Animals A total of 17 adult Rambouillet ewes at 131 (128–133) [median (minimum, maximum)] days gestation, weighing 56 (46, 63) kg. Methods Ewes and fetuses were chronically instrumented with catheters in a maternal jugular vein, maternal carotid artery and fetal femoral artery. Twenty milliliters per kilograms of blood were removed from each ewe over 1 hour. The ewes were then given 20 mL kg?1 of either Oxyglobin Solution (n = 5), hetastarch (n = 6), or autologous whole blood (n = 6) IV. Maternal plasma COP was measured before hemorrhage, after hemorrhage, after replenishment, and 1 and 2 hours later. Fetal plasma COP was measured after maternal hemorrhage and 2 hours after maternal volume replenishment. Results Median COP of all ewes before hemorrhage was 20 (16, 24) mm Hg and after hemorrhage (p < 0.05), decreased to 16 (11, 19) mm Hg. After volume replenishment, the COP of the Oxyglobin Solution group was 22 (21, 25) mm Hg, the autologous whole blood group was 17 (16, 22) mm Hg and the hetastarch group was 20 (17, 21) mm Hg. The COP of the Oxyglobin Solution group was significantly greater (p < 0.05) than the COP of the hetastarch group immediately and 60 minutes after volume replenishment, and greater (p < 0.05) than that of the autologous whole blood group at 60 minutes after volume replenishment. The COP of all the fetuses after maternal hemorrhage was 16 (12, 19) mm Hg and at 120 minutes after maternal volume replenishment was 15 (11, 18) mm Hg. There were no differences in COP between or within any of the fetal groups. Conclusions When used to treat blood loss, Oxyglobin Solution increases plasma COP more than an equal volume of hetastarch in the first hour following administration. Maternal administration of Oxyglobin Solution did not alter fetal COP. Clinical relevance Oxyglobin Solution is a more potent colloid than hetastarch. Oxyglobin Solution did not appear to translocate fluid from the fetal to maternal circulation.  相似文献   

17.
ObjectivesTo evaluate the sedative effects and pharmacokinetics of detomidine gel administered intravaginally to alpacas in comparison with intravenously (IV) administered detomidine.Study designRandomized, crossover, blinded experiment.AnimalsA group of six healthy adult female Huacaya alpacas (70.3 ± 7.9 kg).MethodsAlpacas were studied on two occasions separated by ≥5 days. Treatments were IV detomidine hydrochloride (70 μg kg−1; treatment DET–IV) or detomidine gel (200 μg kg−1; treatment DET–VAG) administered intravaginally. Sedation and heart rate (HR) were evaluated at intervals for 240 minutes. Venous blood was collected at intervals for 360 minutes after treatment for analysis of detomidine, carboxydetomidine and hydroxydetomidine using liquid chromatography–tandem mass spectrometry. Measured variables were compared between treatments and over time using mixed model analysis. Data are presented as the mean ± standard error of the mean, and a p value of <0.05 was considered significant.ResultsOnset of sedation was faster in treatment DET–IV (1.6 ± 0.2 minutes) than in treatment DET–VAG (13.0 ± 2.5 minutes). Time to maximum sedation was shorter in treatment DET–IV (8.3 ± 1.3 minutes) than in treatment DET–VAG (25 ± 4 minutes). Duration of sedation was not different between treatments. There was a significant linear relationship between sedation score and plasma detomidine concentration. HR was less than baseline for 60 and 125 minutes for treatments DET–IV and DET–VAG, respectively. The maximal decrease in HR occurred at 15 minutes for both treatments. The mean maximum plasma concentration of detomidine, time to maximum concentration and bioavailability for treatment DET–VAG were 39.6 ng mL−1, 19.9 minutes and 20%, respectively.Conclusions and clinical relevanceDetomidine administration at the doses studied resulted in moderate sedation when administered IV or intravaginally to alpacas.  相似文献   

18.
The aim of this study was to determine the pharmacokinetics and prostaglandin E2 (PGE2) synthesis inhibiting effects of intravenous (IV) and transdermal (TD) flunixin meglumine in eight adult female Boer goats. A dose of 2.2 mg/kg was administered intravenously (IV) and 3.3 mg/kg administered TD using a cross‐over design. Plasma flunixin concentrations were measured by LC‐MS/MS. Prostaglandin E2 concentrations were determined using a commercially available ELISA. Pharmacokinetic (PK) analysis was performed using noncompartmental methods. Plasma PGE2 concentrations decreased after flunixin meglumine for both routes of administration. Mean λz‐HL after IV administration was 6.032 hr (range 4.735–9.244 hr) resulting from a mean Vz of 584.1 ml/kg (range, 357.1–1,092 ml/kg) and plasma clearance of 67.11 ml kg?1 hr?1 (range, 45.57–82.35 ml kg?1 hr?1). The mean Cmax, Tmax, and λz‐HL for flunixin following TD administration was 0.134 μg/ml (range, 0.050–0.188 μg/ml), 11.41 hr (range, 6.00–36.00 hr), and 43.12 hr (15.98–62.49 hr), respectively. The mean bioavailability for TD flunixin was calculated as 24.76%. The mean 80% inhibitory concentration (IC80) of PGE2 by flunixin meglumine was 0.28 μg/ml (range, 0.08–0.69 μg/ml) and was only achieved with IV formulation of flunixin in this study. The PK results support clinical studies to examine the efficacy of TD flunixin in goats. Determining the systemic effects of flunixin‐mediated PGE2 suppression in goats is also warranted.  相似文献   

19.
Menge, M., Rose, M., Bohland, C., Zschiesche, E., Kilp, S., Metz, W., Allan, M., Röpke, R., Nürnberger, M. Pharmacokinetics of tildipirosin in bovine plasma, lung tissue, and bronchial fluid (from live, nonanesthetized cattle). J. vet. Pharmacol. Therap.  35 , 550–559. The pharmacokinetics of tildipirosin (Zuprevo® 180 mg/mL solution for injection for cattle), a novel 16‐membered macrolide for treatment, control, and prevention of bovine respiratory disease, were investigated in studies collecting blood plasma, lung tissue, and in vivo samples of bronchial fluid (BF) from cattle. After single subcutaneous (s.c.) injection at 4 mg/kg body weight, maximum plasma concentration (Cmax) was 0.7 μg/mL. Tmax was 23 min. Mean residence time from the time of dosing to the time of last measurable concentration (MRTlast) and terminal half‐life (T1/2) was 6 and 9 days, respectively. A strong dose–response relationship with no significant sex effect was shown for both Cmax and area under the plasma concentration–time curve from time 0 to the last sampling time with a quantifiable drug concentration (AUClast) over the range of doses up to 6 mg/kg. Absolute bioavailability was 78.9%. The volume of distribution based on the terminal phase (Vz) was 49.4 L/kg, and the plasma clearance was 144 mL/h/kg. The time–concentration profile of tildipirosin in BF and lung far exceeded those in blood plasma. In lung, tildipirosin concentrations reached 9.2 μg/g at 4 h, peaked at 14.8 μg/g at day 1, and slowly declined to 2.0 μg/g at day 28. In BF, the concentration of tildipirosin reached 1.5 and 3.0 μg/g at 4 and 10 h, maintained a plateau of about 3.5 μg/g between day 1 and 3, and slowly declined to 1.0 at day 21. T1/2 in lung and BF was approximately 10 and 11 days. Tildipirosin is rapidly and extensively distributed to the respiratory tract followed by slow elimination.  相似文献   

20.
ObjectiveTo investigate the cardiorespiratory, nociceptive and endocrine effects of the combination of propofol and remifentanil, in dogs sedated with acepromazine.Study designProspective randomized, blinded, cross-over experimental trial.AnimalsTwelve healthy adult female cross-breed dogs, mean weight 18.4 ± 2.3 kg.MethodsDogs were sedated with intravenous (IV) acepromazine (0.05 mg kg?1) followed by induction of anesthesia with IV propofol (5 mg kg?1). Anesthesia was maintained with IV propofol (0.2 mg kg?1 minute?1) and remifentanil, infused as follows: R1, 0.125 μg kg?1 minute?1; R2, 0.25 μg kg?1 minute?1; and R3, 0.5 μg kg?1 minute?1. The same dogs were administered each dose of remifentanil at 1-week intervals. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (fR), end tidal CO2 (Pe′CO2), arterial hemoglobin O2 saturation, blood gases, and rectal temperature were measured before induction, and 5, 15, 30, 45, 60, 75, 90, and 120 minutes after beginning the infusion. Nociceptive response was investigated by electrical stimulus (50 V, 5 Hz and 10 ms). Blood samples were collected for plasma cortisol measurements. Statistical analysis was performed by anova (p < 0.05).ResultsIn all treatments, HR decreased during anesthesia with increasing doses of remifentanil, and increased significantly immediately after the end of infusion. MAP remained stable during anesthesia (72–98 mmHg). Antinociception was proportional to the remifentanil infusion dose, and was considered satisfactory only with R2 and R3. Plasma cortisol concentration decreased during anesthesia in all treatments. Recovery was smooth and fast in all dogs.Conclusions and clinical relevanceInfusion of 0.25–0.5 μg kg?1 minute?1 remifentanil combined with 0.2 mg kg?1 minute?1 propofol produced little effect on arterial blood pressure and led to a good recovery. The analgesia produced was sufficient to control the nociceptive response applied by electrical stimulation, suggesting that it may be appropriate for performing surgery.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号