Plasma pharmacokinetics of ranitidine HCl in adult horses

Plasma pharmacokinetics of ranitidine HCl were investigated after intravenous (i.v.) and oral (p.o.) administration of 2.2 mg/kg drug to six healthy adult horses. Concentrations of ranitidine were determined using normal-phase, high-performance liquid chromatography. Plasma concentrations of ranitidine HCl declined from a mean of 5175 ng/mL at 5 min to 37 ng/mL at 720 min after i.v. administration. A three-exponent equation, C_p= A₁· e^–k1t+ A₂· e^–k2t+ A₃· e^–k3t, best described data for all horses. Mean values for model-independent values calculated from the last quantifiable time point were: apparent volume of distribution (Vd_ss) = 1.07 L/kg; area under the curve ( AUC ) = 231,000 ng · min/mL; area under the moment curve ( AUMC ) = 26,900,000 ng · min²/mL; mean residence time ( MRT ) = 113 min; and clearance (Cl) = 9.8 mL/min.kg. Following p.o. administration, a two-exponent equation, C_p= A₁· e^–k1t+ A₂· e^–k2t, best described the data for five horses; data for the remaining horse were best described by a three-exponent equation. Mean values of pharmacokinetic values from the p.o. study include: AUC = 59,900 ng · min/mL; AUMC = 10,600,000 ng · min²/mL; mean absorption time ( MAT ) = 58.9 min; T _max= 99.2 min; C _max= 237 ng/mL; and F = 27%.     

Sevoflurane anaesthesia in clinical equine cases: maintenance and recovery

A new inhalant anaesthetic, sevoflurane, was used to maintain anaesthesia in 40 animals (2 mules and 38 horses of 9 breeds) presented for various surgical procedures. Eighteen mares, 11 stallions and 11 geldings underwent 6 orthopaedic and 34 soft tissue operations. Induction of anaesthesia was achieved with combinations of xylazine (0.5–1.1 mg/kg), diazepam (0.03–0.1 mg/kg), butorphanol (0.02 mg/kg), guaifenesin (50–84 mg/kg) and ketamine (1.1 mg/kg). Following tracheal intubation, a surgical plane of anaesthesia was maintained with sevoflurane in oxygen delivered from a precision vaporiser. Temperature, ECG, arterial blood pressure and expired gas composition were monitored. Mechanical ventilation was used in most animals (n=37) because of hypoventilation (P_aCO₂ > 7.31 kPa [55 mmHg]). Following surgery, horses were moved to a recovery room and allowed to recover alone (n=36) or with assistance (n=4). Time to sternal recumbency, standing, the time when satisfactory coordination was present (after standing) and the number of attempts to stand were recorded. The quality of recovery was scored on a 1 (best) to 6 (worst) scale. Mean blood pressures at 30, 60, 90, 120 and 150 min of anaesthesia were 72, 73, 74, 75 and 72 mmHg, respectively. Systolic and diastolic pressures at 30, 60, 90, 120 and 150 min of anaesthesia were 97, 97, 94, 96, 93 and 59, 63, 64, 68, 67 mmHg, respectively. Dobutamine was used in 23 horses to maintain mean arterial blood pressure > 60 mmHg. Mean heart and respiratory rates at 30, 60, 90, 120 and 150 min of anaesthesia were 36, 38, 39, 38 and 38 beats/min, and 9, 8, 8, 8 and 8 breaths/min. Mean duration of anaesthesia was 121 rnin (sd: 56 min), mean time to sternal recumbency was 27 min (sd: 13 min), average time to standing (all horses) was 33 min (sd: 12 min) and time to satisfactory coordination was 44 min (sd: 13 min). Most horses (n=37) received xylazine during recovery (mean dose 0.18 mg/kg iv). The median number of attempts to sternal recumbency and standing were 1.0 (range; 1–7) and 2.0 (range; 1–20), respectively, while the median recovery score was 1.5 (range; 14). The ‘depth’ of anaesthesia was easy to control and recoveries were generally very satisfactory.     

Pharmacokinetic study of dipyrone metabolite 4-MAA in the horse and possible implications for doping control

The pharmacokinetic behaviour of dipyrone metabolite 4-MAA in serum was determined in seven horses of different breeds after a single intravenous dose administration. A biexponential formula was fitted to the serum concentration vs. time data. The median half-life of the elimination phase ( t _1/2β) was 4.85 h (range 5.04 h), the median volume of distribution ( V d_area) was 1.85 L/kg (range 3.2 L/kg) and median of total clearance was 4.0 mL/min/kg (range 2.3 mL/min/kg).     

The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1α and ex vivo endotoxin-induced tumour necrosis factor activity in horses

Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F_1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t _½β) of pentoxifylline was 1.44 h and volume of distribution ( V d_area) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F_1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F_1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.     

Alfaxalone in cyclodextrin for induction and maintenance of anaesthesia in ponies undergoing field castration

Objective  To evaluate the induction and maintenance of anaesthesia using alfaxalone following pre-anaesthetic medication with romifidine and butorphanol in ponies undergoing castration in the field.
Study design  Prospective clinical study.
Animals  Seventeen male ponies weighing 169 ± 29 kg.
Methods  The ponies were sedated with romifidine and butorphanol intravenously (IV). Induction time was recorded following administration of alfaxalone 1 mg kg⁻¹ and diazepam 0.02 mg kg⁻¹ IV. If movement during surgery occurred, alfaxalone 0.2 mg kg⁻¹ was administered IV. The quality of anaesthetic induction, and recovery were scored on a subjective scale of 1 (good) to 5 (poor). The number of attempts to attain sternal recumbency and standing, quality of recovery and times from induction to end of surgery, first head lift, sternal recumbency and standing were recorded.
Results  Induction quality was good [median score (range) 1 (1–3)] with a mean ± SD time of 29 ± 6 seconds taken to achieve lateral recumbency. Ten ponies required incremental doses of alfaxalone during surgery. Mean times to the end of surgery, first head lift, sternal recumbency and standing were 26 ± 9 minutes, 31 ± 9 minutes, 33 ± 9 minutes and 34 ± 9 minutes respectively. The number of attempts to attain sternal recumbency was 1(1–1) and to attain standing was 1(1–2). Quality of recovery was good, with a recovery score of 1(1–2).
Conclusions and clinical relevance  Alfaxalone provided smooth induction and recovery characteristics and was considered suitable for maintenance of anaesthesia for castration in ponies.     

The pharmacokinetics of furosemide in anaesthetized horses after bilateral ureteral ligation

The pharmacokinetics of furosemide were investigated in anaesthetized horses with bilateral ureteral ligation (BUL) with ( n  = 5) or without ( n  = 5) premedication with phenylbutazone. Horses were administered an intravenous (i.v.) bolus dose of furosemide (1 mg/kg) 6090 min after BUL. Plasma samples collected up to 3 h after drug administration were analysed by a validated high performance liquid chromatography method. Median plasma clearance ( CL _p) of furosemide in anaesthetized horses with BUL was 1.4 mL/min/kg. Apparent steady state volume of distribution ( V d_ss) ranged from 169 to 880 mL/kg and the elimination half life ( t _½) ranged from 83 min to 209 h.   No differences in plasma concentration or kinetic parameter estimates were observed when phenylbutazone was administered before furosemide administration. BUL markedly reduces the elimination of furosemide in horses and models the potential effects that severe changes in kidney function may have on drug kinetics in horses.     

Comparative pharmacokinetics of meloxicam in clinically normal horses and donkeys

OBJECTIVE: To determine the disposition of a bolus of meloxicam (administered IV) in horses and donkeys (Equus asinus) and compare the relative pharmacokinetic variables between the species. ANIMALS: 5 clinically normal horses and 5 clinically normal donkeys. PROCEDURES: Blood samples were collected before and after IV administration of a bolus of meloxicam (0.6 mg/kg). Serum meloxicam concentrations were determined in triplicate via high-performance liquid chromatography. The serum concentration-time curve for each horse and donkey was analyzed separately to estimate standard noncompartmental pharmacokinetic variables. RESULTS: In horses and donkeys, mean +/- SD area under the curve was 18.8 +/- 7.31 microg/mL/h and 4.6 +/- 2.55 microg/mL/h, respectively; mean residence time (MRT) was 9.6 +/- 9.24 hours and 0.6 +/- 0.36 hours, respectively. Total body clearance (CL(T)) was 34.7 +/- 9.21 mL/kg/h in horses and 187.9 +/- 147.26 mL/kg/h in donkeys. Volume of distribution at steady state (VD(SS)) was 270 +/- 160.5 mL/kg in horses and 93.2 +/- 33.74 mL/kg in donkeys. All values, except VD(SS), were significantly different between donkeys and horses. CONCLUSIONS AND CLINICAL RELEVANCE: The small VD(SS) of meloxicam in horses and donkeys (attributed to high protein binding) was similar to values determined for other nonsteroidal anti-inflammatory drugs. Compared with other species, horses had a much shorter MRT and greater CL(T) for meloxicam, indicating a rapid elimination of the drug from plasma; the even shorter MRT and greater CL(T) of meloxicam in donkeys, compared with horses, may make the use of the drug in this species impractical.     

Evaluation of xylazine and ketamine for total intravenous anesthesia in horses

OBJECTIVE: To evaluate the use of xylazine and ketamine for total i.v. anesthesia in horses. ANIMALS: 8 horses. PROCEDURE: Anesthetic induction was performed on 4 occasions in each horse with xylazine (0.75 mg/kg, i.v.), guaifenesin (75 mg/kg, i.v.), and ketamine (2 mg/kg, i.v.). Intravenous infusions of xylazine and ketamine were then started by use of 1 of 6 treatments as follows for which 35, 90, 120, and 150 represent infusion dosages (microg/kg/min) and X and K represent xylazine and ketamine, respectively: X35 + K90 with 100% inspired oxygen (O2), X35 + K120-(O2), X35 + K150-(O2), X70 + K90-(O2), K150-(O2), and X35 + K120 with a 21% fraction of inspired oxygen (ie, air). Cardiopulmonary measurements were performed. Response to a noxious electrical stimulus was observed at 20, 40, and 60 minutes after induction. Times to achieve sternal recumbency and standing were recorded. Quality of sedation, induction, and recovery to sternal recumbency and standing were subjectively evaluated. RESULTS: Heart rate and cardiac index were higher and total peripheral resistance lower in K150-(O2) and X35 + K120-air groups. The mean arterial pressure was highest in the X35 + K120-air group and lowest in the K150-(O2) group (125 +/- 6 vs 85 +/- 8 at 20 minutes, respectively). Mean Pa(O2) was lowest in the X35 + K120-air group. Times to sternal recumbency and standing were shortest for horses receiving K150-(O2) (23 +/- 6 minutes and 33 +/- 8 minutes, respectively) and longest for those receiving X70 + K90-(O2) (58 +/- 28 minutes and 69 +/- 27 minutes, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: Infusions of xylazine and ketamine may be used with oxygen supplementation to maintain 60 minutes of anesthesia in healthy adult horses.     

Pharmacokinetics of cefoperazone in horses

The pharmacokinetics and bioavailabilty of cefoperazone (CPZ) were studied following intravenous (IV) and intramuscular (IM) administration of single doses (30 mg/kg) to horses. Concentrations in serum, urine and synovial fluid samples were measured following IV administration. CPZ concentrations in serum, synovial fluid and spongy bone samples were measured following IM administration. After IV administration a rapid distribution phase ( t _1/2(α):4.22 ± 2.73 min) was followed by a slower elimination phase ( t 1/2(β) 0.77 ± 0.19 h). The apparent volume of distribution was 0.68 ± 0.10 L/kg. Mean synovial fluid peak concentration was 5.76 ± 0.74 μg/mL. After IM administration a bioavailability of 42.00±5.33% was obtained. Half-life of absorption was 2.51 ± 0.72 min and t _1/2(β) was 1.52±0.15 h. The mean synovial fluid and spongy bone peak concentrations at 2 h after IM administration were 2.91±0.85 μg/mL and 5.56±0.70 μg/mL, respectively.     

Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (C_S0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC₉₀) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time-dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC_0-12/MIC₉₀ ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC_0-12/MIC₉₀ ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.     

Effects of 5% and 10% Guaifenesin Infusion on Equine Vascular Endothelium

Twelve horses of various breeds and either sex were anesthetized with xylazine and ketamine injected into a median or lateral thoracic vein. During anesthesia, with the horse in sternal recumbency, a 14-gauge, 8.9 cm catheter was inserted into each jugular vein by using aseptic technique. Guaifenesin in water (100 mg/kg or a maximum dose of 50 grams) was infused into one jugular vein and an equal volume of 0.9% saline solution was infused into the other jugular vein. Seven horses received 10% guaifenesin, and five horses received 5% guaifenesin. The catheters were removed before the horses recovered from anesthesia. The horses were euthanatized approximately 48 hours later, and the jugular veins were removed for histologic examination. Adherent thrombus material was observed in all veins exposed to 10% guaifenesin and in one vein exposed to 5% guaifenesin. No evidence of thrombus was observed in four veins infused with 5% guaifenesin or in those infused with saline solution. These findings are of particular significance with horses at increased risk for thrombosis or thrombophlebitis.     

Prolongation of anesthesia with xylazine, ketamine, and guaifenesin in horses: 64 cases (1986-1989)

On 74 occasions, 54 horses and 6 foals were anesthetized with xylazine and ketamine or xylazine, guaifenesin, and ketamine, with or without butorphanol. On 64 occasions, anesthesia was prolonged for up to 70 minutes (34 +/- 15 min) by administration of 1 to 9 supplemental IV injections of xylazine and ketamine at approximately a third the initial dosage. All horses except 5 were positioned in lateral recumbency, and oxygen was insufflated. In adult horses, the time from induction of anesthesia to the first supplemental xylazine and ketamine injection was 13 +/- 4 minutes and the time between supplemental injections was 12.1 +/- 3.7 minutes. These results were consistent with predicted plasma ketamine concentration calculated from previously published pharmacokinetic data for ketamine in horses. Respiratory and heart rates and coccygeal artery pressure remained consistent for the duration of anesthesia. The average interval between the last injection of ketamine and assumption of sternal position was approximately 30 minutes, and was the same regardless of the number of supplemental injections. The time to standing was significantly longer (P less than 0.05) in horses given 2 supplemental injections, compared with those not given any or only given 1, but was not longer in horses given 3 supplemental injections. Recovery was considered unsatisfactory in 5 horses, but did not appear to be related to prolongation of anesthesia.     

Influence of closure of the reticular groove on the bioavailability and disposition kinetics of meclofenamate in sheep

Sodium meclofenamate is a non-steroidal anti-inflammatory drug with anaphylactic protective activity in cattle. The objectives of this study were to describe the pharmacokinetic behaviour of sodium meclofenamate after intravenous and oral administration to sheep and to determine the influence of closure of the reticular groove on the bioavailability of the drug. Sodium meclofenamate was administered by the intravenous (2.2 mg/kg) and oral (20 mg/kg) routes to sheep (n = 6). During the oral study the reticular groove was closed by intravenous administration of lysine vasopressin (0.3 IU/kg) or left open (saline solution). The closure of the reticular groove was assessed by determination of the blood glucose curves after oral administration of a glucose solution. After intravenous administration of meclofenamate, the distribution and elimination half-lives of the drug were 7.2 min and 542 min respectively, V_ss was 1.68 L/kg and Cl_B was 2.47 mL/min kg. Two different patterns of the plasma concentration curves were observed after oral administration of sodium meclofenamate. When the reticular groove was closed, two peaks were observed ( t _max-2 12-15 min, C _max-1 3.30-24.01 μg/mL; and t _max-2', 52.50-75 min, C _max-2' 6.45-11.08 μg/mL).     

Pharmacokinetics, bioavailability and dosage regimen of sulphadiazine (SDZ) in camels (Camelus dromedarius)

The pharmacokinetics of sulphadiazine (SDZ) (100 mg/kg, body weight) were investigated in six camels ( Camelus dromedarius ) after intravenous (i.v.) and oral (p.o.) administration. Following i.v. administration, the overall elimination rate constant (β) was 0.029±0.001/h and the half-life ( t _½β) was 23.14±1.06 h. The apparent volume of distribution ( V d_(area)) was 0.790±0.075 L/kg and the total body clearance ( Cl _B) was 23.29±2.50 mL/h/kg. After p.o. administration, SDZ reached a peak plasma concentration ( C _max(cal.)) of 62.93±2.79 μg/mL at a post injection time of ( T _max(cal.)) 22.98±0.83 h. The elimination half-life was 19.79±1.22 h, not significantly different from that obtained by the i.v. route. The mean absorption rate constant (K_a) was 0.056±0.002 h⁻¹ and the mean absorption half-life ( t _½Ka) was 12.33±0.37 h. The mean availability ( F ) of sulphadiazine was 88.2±6.2%.
  To achieve and maintain therapeutically satisfactory plasma SDZ levels of 50 μg/mL, the priming and maintenance doses would be 80 mg/kg and 40 mg/kg intravenously and 90 mg/kg and 45 mg/kg orally, respectively, to be repeated at 24 h intervals.     

Comparison of recoveries from anesthesia of horses placed on a rapidly inflating-deflating air pillow or the floor of a padded stall

OBJECTIVE: To compare recoveries from anesthesia of horses placed on a conventional padded stall floor or on a specially designed air pillow. DESIGN: Prospective study. ANIMALS: 409 horses (> 1 year old) that were anesthetized for surgical procedures during a 37-month period. PROCEDURES: By random allocation, horses were allowed to recover from anesthesia in either a foammat-padded recovery stall or an identical recovery stall equipped with a rapidly inflating-deflating air pillow. All recoveries were videotaped for subsequent analysis by an independent evaluator. Times to first movement, first attempt to attain sternal recumbency, attainment of sternal recumbency, first attempt to stand, and successful standing were recorded. The numbers of attempts before achieving sternal recumbency and standing were counted, and scores for quality of standing and overall recovery were assigned. Recovery-related variables were compared between groups. RESULTS: Compared with horses allowed to recover in a conventional manner, horses that recovered from anesthesia on the air pillow had a significantly longer rest period before attempting to attain sternal recumbency and rise to standing. Once the pillow was deflated, horses were able to stand after significantly fewer attempts and the quality of their standing was significantly better. Between the 2 groups of horses, there was no significant difference in overall recovery quality scores. The air pillow and padded floor systems were equally safe. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that use of a rapidly inflating-deflating air pillow promotes a longer period of recumbency and a better quality of standing after anesthesia in horses.     

Pharmacokinetics of cisapride in the horse

The purpose of this study was to determine the pharmacokinetics and absolute bioavailability of cisapride after intravenous (i.v.) and intragastric (i.g.) administration in healthy, adult horses. Five animals received single doses of 0.1 mg/kg, 0.2 mg/kg and 0.4 mg/kg cisapride by the i.g. route in an open, randomized fashion on different occasions separated by a washout period of at least 48 h. Four of these horses were also given a single i.v. dose of 0.1 mg/kg cisapride. Jugular venous blood was collected periodically up to 24 h after dosing. Plasma cisapride concentrations were measured by high-performance liquid chromatography.
  There was considerable inter individual variability in pharmacokinetic parameters. The mean (SD) values for systemic clearance ( Cl ) and steady-state volume of distribution ( V ss) were 494 (43.6) mL/h/kg and 1471 (578) mL/kg, respectively. Although the rate of cisapride absorption was quite rapid, only about half the i.g. dose was absorbed systemically. The average terminal half-life ( t _½) calculated over three i.g. doses was 2.06 h and that for i.v. administration was 2.12 h. The pharmacokinetics of cisapride from 0.1 mg/kg to 0.4 mg/kg were independent of the i.g. dose.     

The effect of inflammation on the disposition of phenylbutazone in Thoroughbred horses

The effect of inflammation on the disposition of phenylbutazone (PBZ) was investigated in Thoroughbred horses. An initial study ( n = 5) in which PBZ (8.8 mg/kg) was injected intravenously twice, 5 weeks apart, suggested that the administration of PBZ would not affect the plasma kinetics of a subsequent dose. Two other groups of horses were given PBZ at either 8.8 mg/kg ( n = 5) or 4.4 mg/kg ( n = 4). Soft tissue inflammation was then induced by the injection of Freud's adjuvant and the administration of PBZ was repeated at a dose level equivalent to, but five weeks later than, the initial dose. Inflammation did not appear to affect the plasma kinetics or the urinary excretion of PBZ and its metabolites, oxyphenbutazone (OPBZ) or hydroxyphenylbutazone (OHPBZ) when PBZ was administered at 8.8 mg/kg. However, small but significant increases ( P <0.05) in total body clearance ( CL _B; 29.2 ± 3.9 vs. 43.8 ± 8.1 mL/ h-kg) and the volume of distribution, calculated by area ( V _d(area); 0.18 ± 0.05 vs. 0.25 ± 0.03 L/kg) or at steady-state ( V _d(SS); 0.17±0.04 vs. 0.25 ± 0.03 L/ kg), were obtained in horses after adjuvant injection, compared to controls, when PBZ was administered at 4.4 mg/kg which corresponded to relatively higher tissues concentrations and lower plasma concentrations (calculated) at the time of maximum peripheral PBZ concentration. Soft tissue inflammation also induced a significantly ( P <0.05) higher amount of OPBZ in the urine 18 h after PBZ administration but the total urinary excretion of analytes over 48 h was unchanged. These results have possible implications regarding the administration of PBZ to the horse close to race-day.     

Disposition of metronidazole in hens (Gallus gallus) and quails (Coturnix coturnix japonica): pharmacokinetics and whole-body autoradiography

Hens were given single intravenous or oral doses (30 mg/kg body weight) of metronidazole and the plasma concentrations of the drug were determined by high-performance liquid chromatography (HPLC) at intervals from 10 min to 24 h after drug administration. Pharmacokinetic variables were calculated by the Lagrange algorithm technique. The elimination half-life ( t _1/2β) after the intravenous injection was 4.2 ± 0.5 h, the volume of distribution ( V _d(ss)) 1.1±0.2 L/kg and the total body clearance ( Cl _B) 131.2 ± 20 mL/h.kg. Oral bioavailability of the metronidazole was 78 ± 16%. The plasma maximum concentration ( C _max) 31.9 ± 2.3 μg/mL was reached 2 h after the oral administration and the oral elimination half-life ( t ₁/2β) was 4.7 ± 0.2 h. The binding of metronidazole to proteins in hen plasma was very low (less than 3%). Whole body autoradiography of [³H] metronidazole in hens and quails showed an even distribution of labelled material in various tissues at short survival intervals (1-4 h) after oral or intravenous administration. A high labelling was seen in the contents of the small and large intestines. In the laying quails a labelling was also seen in the albumen and in a ring in the periphery of the yolk at long survival intervals. Our results show that a concentration twofold above the MIC is maintained in the plasma of hens for at least 12 h at an oral dose of 30 mg/kg metronidazole.     

The recovery of horses from inhalant anesthesia: a comparison of halothane and isoflurane

Objective— Recovery is one of the more precarious phases of equine general anesthesia. The quality and rate of recovery of horses from halothane and isoflurane anesthesia were compared to determine differences in the characteristics of emergence from these commonly used inhalant anesthetics. Experimental Design— Prospective, randomized blinded clinical trial. Sample Population— A total of 96 Thoroughbred and 3 Standardbred racehorses admitted for elective distal forelimb arthroscopy. Methods— All horses were premedicated with intravenous xylazine, induced with guaifenesin and ketamine, and maintained on a large animal circle system fitted with an out of the circle, agent specific vaporizer. Recoveries were managed by a blinded scorer with a standardized protocol. A 10 category scoring system was used to assess each horse's overall attitude, purposeful activity, muscle coordination, strength and balance from the time of arrival in recovery to standing. Times to extubation, sternal recumbency and standing were recorded. Median recovery scores and mean times to extubation, sternal and standing were compared using the Mann‐Whitney U test and student's t test, respectively. Results— The median score for horses recovering from halothane was lower (20.0; range, 10 to 57) than that for horses recovering from isoflurane (27.5; range, 10 to 55). Horses in the two groups were extubated at similar mean times (halothane, 11.3 ± 5.5 and isoflurane, 9.5 ± 5.2 minutes ) but horses recovering from isoflurane achieved sternal recumbency (halothane, 37.7 ± 12.1 and isoflurane, 24.7 ± 8.8 minutes ) and stood (halothane, 40.6 ± 12.9 and isoflurane, 27.6 ± 9.6 minutes ) sooner than those recovering from halothane. Conclusions— The recovery of horses from isoflurane anesthesia was more rapid but less composed than that from halothane. Clinical Relevance— The quality of recovery following isoflurane was worse than after halothane anesthesia using the criteria chosen for this study. However, the range of recovery scores was similar for both groups and all horses recovered without significant injury.     

A comparison of three combinations of injectable anesthetics in miniature donkeys

Objective To compare three combinations of injectable anesthetics in miniature donkeys for quality of induction, recovery, muscle relaxation, cardiopulmonary changes during anesthesia and duration of recumbency. Design Prospective, randomized experimental study. Animals Six miniature donkeys (< 90 cm in height at the withers) weighing 92–127 kg were used. Materials and methods The drug combinations were: xylazine?butorphanol?ketamine (XBK), xylazine?butorphanol?tiletamine?zolazepam (XBT) and xylazine?propofol (XP). Each miniature donkey was anesthetized with each combination at 1‐week intervals in random order. Heart and respiratory rates, indirect blood pressure and temperature were measured before and at 5‐minute intervals during recumbency. Arterial blood samples were drawn for blood‐gas analysis before and at 5, 15 and 30 minutes of anesthesia when samples could be collected. Recumbency time to sternal and time to standing were recorded and a subjective evaluation of induction, muscle relaxation and recovery were made. Results Mean recumbency time ± SD was 14.7 ± 9.4, 33.8 ± 6.3 and 14.6 ± 1.9 minutes with XBK, XBT and XP, respectively. Mean time to standing ± SD was 28.4 ± 11.3, 43.7 ± 7.2 and 26.3 ± 2.9 minutes with XBK, XBT and XP, respectively. Heart and respiratory rates and blood pressures varied from baseline but were always within normal ranges. Hemoglobin saturation, pH and PaO₂ tended to be lower with these doses of XBT and XP. Conclusions and clinical relevance Overall quality of anesthesia was poor with XBK. At the doses used this combination did not provide sufficient anesthesia compared with the combinations of XBT and XP, which appeared to provide acceptable anesthesia of short duration in miniature donkeys.