Pharmacokinetics of sulfamethoxazole and trimethoprim in donkeys, mules, and horses

OBJECTIVE: To compare serum disposition of sulfamethoxazole and trimethoprim after IV administration to donkeys, mules, and horses. ANIMALS: 5 donkeys, 5 mules, and 3 horses. PROCEDURE: Blood samples were collected before (time 0) and 5, 15, 30, and 45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10, and 24 hours after IV administration of sulfamethoxazole (12.5 mg/kg) and trimethoprim (2.5 mg/kg). Serum was analyzed in triplicate with high-performance liquid chromatography for determination of sulfamethoxazole and trimethoprim concentrations. Serum concentration-time curve for each animal was analyzed separately to estimate noncompartmental pharmacokinetic variables. RESULTS: Clearance of trimethoprim and sulfamethoxazole in donkeys was significantly faster than in mules or horses. In donkeys, mean residence time (MRT) of sulfamethoxazole (2.5 hours) was less than half the MRT in mules (6.2 hours); MRT of trimethoprim in donkeys (0.8 hours) was half that in horses (1.5 hours). Volume of distribution at steady state (Vdss) for sulfamethoxazole did not differ, but Vdss of trimethoprim was significantly greater in horses than mules or donkeys. Area under the curve for sulfamethoxazole and trimethoprim was higher in mules than in horses or donkeys. CONCLUSIONS AND CLINICAL RELEVANCE: Dosing intervals for IV administration of trimethoprim-sulfamethoxazole in horses may not be appropriate for use in donkeys or mules. Donkeys eliminate the drugs rapidly, compared with horses. Ratios of trimethoprim and sulfamethoxazole optimum for antibacterial activity are maintained for only a short duration in horses, donkeys, and mules.     

Pharmacokinetics of R(-) and S(+) carprofen after administration of racemic carprofen in donkeys and horses

OBJECTIVE: To compare plasma disposition of the R(-) and S(+) enantiomers of carprofen after IV administration of a bolus dose to donkeys and horses. ANIMALS: 5 clinically normal donkeys and 3 clinically normal horses. PROCEDURE: Blood samples were collected from all animals at time 0 (before) and at 10, 15, 20, 30, and 45 minutes and 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 24, 28, 32, and 48 hours after IV administration of a bolus of carprofen (0.7 mg/kg). Plasma was analyzed in triplicate via high-performance liquid chromatography to determine the concentrations of the carprofen enantiomers. A plasma concentrationtime curve for each donkey and horse was analyzed separately to estimate noncompartmental pharmacokinetic variables. RESULTS: In donkeys and horses, the area under the plasma concentration versus time curve (AUC) was greater for the R(-) carprofen enantiomer than it was for the S(+) carprofen enantiomer. For the R(-) carprofen enantiomer, the AUC and mean residence time (MRT) were significantly less and total body clearance (CIT) was significantly greater in horses, compared with donkeys. For the S(+) carprofen enantiomer, AUC and MRT were significantly less and CIT and apparent volume of distribution at steady state were significantly greater in horses, compared with donkeys. CONCLUSIONS AND CLINICAL RELEVANCE: Results have suggested that the dosing intervals for carprofen that are used in horses may not be appropriate for use in donkeys.     

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.     

Post mortem survey of peripheral dental caries in 510 Swedish horses

Reasons for performing study: Peripheral caries (PC) of equine teeth is a poorly described disorder that can cause serious clinical problems if it progresses. Objectives: To assess the prevalence, sites and severity of PC in a population of Swedish horses. Methods: A post mortem study of 510 equine skulls was performed in 2 Swedish equine abattoirs. Results: PC only affected the cheek teeth (CT) and was present in 6.1% (31/510) of skulls. It affected mainly the peripheral cementum, and 87% of PC in the 29 affected mature horses occurred in the 3 caudal CT (Triadan 09‐11). Concurrent infundibular caries involving most maxillary CT (mean 9.7/skull) was present in 32% of skulls affected with PC. Trotting horses (mean age 8.1 years) believed to be on a high concentrate and silage diet were preferentially affected with PC in this population. Food was usually tightly adherent to the PC lesions and this feature may have promoted the progression of the disease. Significantly increased levels of diastemata were present in PC‐affected horses, and periodontal disease was present in areas adjacent to some PC lesions. Conclusions: PC is a relatively common disorder of horses under certain management conditions that can progress to cause serious dental disorders, especially if concurrent, widespread infundibular caries is present. Potential relevance: Equine clinicians should be aware of this significant dental disorder and research into its aetiopathogenesis, possible prevention and treatment are required.     

Pharmacology and therapeutics in donkeys

Therapeutics are often administered to donkeys based on dosage and intervals recommended for horses because very few drugs have donkey‐specific label indications. Yet differences between donkeys and horses in drug distribution, metabolism and elimination have been noted for most therapeutic agents studied. These differences can be partially explained by the donkey's unique physiology. Since their ancestors evolved in a desert environment, the modern donkey exhibits qualities that allow them to tolerate dehydration better than the horse and recover more quickly from its effects. Fluid balance and body water compartment partitioning differ from the horse and may have implications regarding drug distribution. Since donkeys are preferential browsers, differences in diet may have influenced evolutionary differences in metabolic disposition of drugs. It is important to acknowledge these differences when designing dose regimes for donkeys based on horse protocols in order to avoid either lack of efficacy or toxicity.     

Donkey dental anatomy. Part 2: Histological and scanning electron microscopic examinations

Ten normal cheek teeth (CT) were extracted at post mortem from donkeys that died or were euthanased for humane reasons. Decalcified histology was performed on three sections (sub-occlusal, mid-tooth and pre-apical) of each tooth, and undecalcified histology undertaken on sub-occlusal sections of the same teeth. The normal histological anatomy of primary, regular and irregular secondary dentine was found to be similar to that of the horse, with no tertiary dentine present. Undecalcified histology demonstrated the normal enamel histology, including the presence of enamel spindles. Scanning electron microscopy was performed on mid-tooth sections of five maxillary CT, five mandibular CT and two incisors. The ultrastructural anatomy of primary and secondary dentine, and equine enamel types-1, -2 and -3 (as described in horses) were identified in donkey teeth. Histological and ultrastructural donkey dental anatomy was found to be very similar to equine dental anatomy with only a few quantitative differences observed.     

Differential responses of Equus caballus and Equus asinus to infection with two pathogenic strains of equine infectious anemia virus

Most in vivo studies with equine infectious anemia virus (EIAV) have been performed in horses and ponies (Equus caballus) with little published information available detailing the clinical responses of donkeys (Equus asinus) to infection with this virus. Consequently, donkeys were inoculated with two strains of EIAV (EIAV(PV) and EIAV(WY)) which have been documented to produce disease in E. caballus. Four ponies, 561, 562, 564 and 567 and two donkeys, 3 and 5 were infected with EIAV(PV) and one horse (94-10) and one donkey (4) were infected with EIAV(WY). Although the horse and ponies all experienced clinical signs of disease, which in some cases were severe, the donkeys remained asymptomatic throughout a 365-day observation period, except for mild transient reductions in platelet counts. The results from serological assays, virus isolation from plasma and detection of plasma-associated viral RNA by RT-PCR, indicated that initial replication of EIAV(PV) and EIAV(WY) was lower in donkeys than in horses and ponies. This conclusion was confirmed using competitive RT-PCR, in which viral RNA levels in the plasma of EIAV(PV)-infected ponies was up to 100,000-fold higher than in infected donkeys during the first 20 days post-infection (dpi). Similar results were obtained in the EIAV(WY)-infected animals, in which viral RNA burdens in the donkey at 20 dpi were 1000-fold less than in the horse. However, infection of donkey and horse monocyte-derived macrophage cultures with EIAV(PV) demonstrated that these cells in vitro were equally susceptible to virus-induced cytopathic effects and yielded similar levels of progeny virus. This result suggests that factors other than host cell permissiveness mediate the clinical differences observed between horses and donkeys infected with EIAV(PV) or EIAV(WY).     

Prevalence of lungworm D. arnfieldi (Cobbold 1884) in donkeys in Denmark and in horses in herds together with donkeys (author's transl)

During a 5 months' period from January to May 1981 faecal samples of 176 donkeys from 59 herds all over the country were examined at the Institute of internal medicine, The Royal Veterinary and Agricultural University, Copenhagen. In addition, the investigation also included 106 horses from 30 of the donkey herds and 34 horses hospitalized with symptoms of dyspnoea and chronic coughing. In all, 87.5% of the donkeys were shown to excrete D. arnfieldi larvae, often in very high numbers, and the larval excretion was the only symptom of lungworm infection. There was no significant correlation between larval excretion and age, sex or herd size. In horses, the frequency of D. arnfieldi infection was approximately the same in the horses from donkey herds and in horses hospitalized due to chronic cough (10.4% and 8.8% resp.). In contrast to the donkeys, the infection in horses was always accompanied by dyspnoea and coughing.     

Pharmacokinetics of flunixin meglumine in donkeys, mules, and horses

OBJECTIVE: To compare serum disposition of flunixin meglumine after i.v. administration of a bolus to horses, donkeys, and mules. ANIMALS: 3 clinically normal horses, 5 clinically normal donkeys, and 5 clinically normal mules. PROCEDURE: Blood samples were collected at time zero (before) and 5, 10, 15, 30, and 45 minutes, and at 1, 1.25, 1.5, 1.75, 2, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, and 8 hours after i.v. administration of a bolus of flunixin meglumine (1.1 mg/kg of body weight). Serum was analyzed in duplicate by the use of high-performance liquid chromatography for determination of flunixin meglumine concentrations. The serum concentration-time curve for each horse, donkey, and mule were analyzed separately to estimate noncompartmental pharmacokinetic variables RESULTS: Mean (+/-SD) area under the curve for donkeys (646 +/- 148 minute x microg/ml) was significantly less than for horses (976 +/- 168 minute x microg/ml) or for mules (860 +/- 343 minute x microg/ml). Mean residence time for donkeys (54.6 +/- 7 minutes) was significantly less than for horses (110 +/- 24 minutes) or for mules (93 +/- 30 minutes). Mean total body clearance for donkeys (1.78 +/- 0.5 ml/kg/h) was significantly different from that for horses (1.14 +/- 0.18 ml/kg/h) but not from that for mules (1.4 +/- 0.5 ml/kg/h). Significant differences were not found between horses and mules for any pharmacokinetic variable. CONCLUSION AND CLINICAL RELEVANCE: Significant differences exist with regard to serum disposition of flunixin meglumine in donkeys, compared with that for horses and mules. Consequently, flunixin meglumine dosing regimens used in horses may be inappropriate for use in donkeys.     

The association analysis between Cytb polymorphism and growth traits in three Chinese donkey breeds

The aim of this study was to investigate the effects of haplotypes in Cytb (Cytochrome b) gene on growth traits in three Chinese donkey breeds, Yunnan donkey (YN), Dezhou donkey (DZ) and Liangzhou donkey (LZ). The samples were genotyped for the Cytb gene by single strand conformation polymorphism (SSCP), and association analysis was conducted with growth traits. The results show that in most cases the effects of the gene on growth traits were not significant and that for the three different donkey breeds, the effects of the gene are different. For YN donkeys, there was a significant effect of the gene on the rump width (P < 0.05) and the effect of genotype AA was larger than that of BB genotype (1.6 cm and 5.4% of the trait mean in YN donkeys, P < 0.05). For DZ donkeys, the effect of gene on body height was significant (P < 0.05). The results also verify that the SSCPs are caused by two cytosine to thymine and one guanine to adenine transitions, corresponding to amino acid substitutions of leucine for proline (L ↔ P) and isoleucine for valine (I ↔ V).     

Analysis of Behaviors Observed During Mechanical Nociceptive Threshold Testing in Donkeys and Horses

The aims of the study were to analyze and compare behaviors in horses and donkeys observed during nociceptive threshold tests with a mechanical stimulus applied to the limb. The purpose was to identify end point behaviors suggesting the animals had perceived the stimulus to be noxious. Six male castrated horses (aged 3–4 years, weighing 415–503 kg) and eight castrated male donkeys (aged 4–9 years, weighing 152.5–170.5 kg) were studied. Video data recorded during mechanical nociceptive threshold test were analyzed by a single observer. Behaviors were classified into short-duration event behaviors and longer duration activity/state behaviors. Frequency of behaviors within a test (event behaviors) and percentage time spent during the test (activity/state behaviors) were calculated. Data were compared between horses and donkeys using Mann–Whitney tests (nonparametric data) or t-test (parametric data). Significance was taken as P < .05. Behaviors during the tests were observed which could indicate the animals perceived the stimulus as noxious. These included flattening ears back against the head, and turning the head (horses) and chewing (donkeys) although these were not consistent across both species. Foot lifts were often preceded by other behaviors which suggests that the foot lift was not purely a reflex withdrawal response. A shift in weight toward the contralateral limb was a consistent prodromal sign for an end point foot lift.     

Lungworm infection (Dictyocaulus arnfieldi) of horses and donkeys.

Dictyocaulus arnfieldi (Cobbold 1884) infects the respiratory tract of horses, donkeys, mules, hinnies and zebra. A review of the literature has been given by Round (1972). In the western hemisphere it is popularly believed that donkeys are the natural host and that horses become infected by association with infected donkeys. There is scant documentary evidence for this and, in the Soviet Union, patent infections may reach 70 per cent without mention of donkey association (Koulikov 1935, Borovkova 1948, Akramovskii 1952a). Poynter (1963) considered the infection to be rare in the United Kingdom although cases had been reported by Fletcher (1960) and Holmes (1960). The lack of precise data on this parasite has led to the assumption that it behaves like D filaria and D viviparaus of ruminants. Studies made in the United Kingdom have shown that there are some important differences (Round, 1972).     

泌乳驴的日粮蛋白水平对驴驹生长发育的影响

试验旨在研究泌乳驴的日粮蛋白水平对驴驹生长发育的影响.选取健康、体况良好的5岁龄、胎次(1.9±0.4)胎、体重(240±30)kg、泌乳日期(29±5)d的带驹德州三粉驴24头,分为3个处理组(H、M、L组),饲喂蛋白水平分别为13.18％、12.22％和11.34％的日粮.每个处理组4个重复,每个重复2头驴.正式试...     

Clinical and pathologic findings in donkeys with hypothermia: 10 cases (1988-1998)

OBJECTIVE: To describe clinical signs and clinicopathologic findings in donkeys with hypothermia. DESIGN: Retrospective study. ANIMALS: 10 hypothermic donkeys. PROCEDURE: Information on signalment, history, physical examination findings, results of diagnostic tests, treatments, and necropsy findings was extracted from medical records of all donkeys with hypothermia between 1988 and 1998 and compared with information from medical records of all normothermic donkeys and hypothermic horses admitted to the hospital during the same period. RESULTS: Donkeys were more likely to be hypothermic than horses. The mean age of hypothermic donkeys was 6 years (range, 7 months to 11 years), compared with 4.2 years (range, < 1 month to 15 years) for normothermic donkeys; this difference was not significant. Ten of 12 horses with hypothermia were neonates; there were no hypothermic neonatal donkeys. At admission, 7 of 8 hypothermic donkeys were in good body condition and all hypothermic donkeys were weak. Six hypothermic donkeys were able to maintain sternal recumbency, 1 remained in lateral recumbency, and 3 were able to stand. Of the 10 hypothermic donkeys, 2 survived, 1 died, and 7 were euthanatized. Histologically, the thyroid glands from 4 of 5 hypothermic donkeys appeared abnormal and were similar to those of foals with hypothyroidism. During the months that hypothermic donkeys were admitted, there was not a significant difference in environmental temperatures on days of admission between hypothermic and normothermic donkeys. CONCLUSIONS AND CLINICAL RELEVANCE: Hypothermia is a problem in donkeys during cold winter months, and may not be secondary to other disease or related to diet or management.     

马、驴主要经济性状功能基因研究进展

马、驴是重要的草食家畜,在人类的历史变迁和生产生活中扮演重要角色。马、驴的初始功能主要以役用为主,多用于乘骑或驮运物品。随着机械化程度和交通方式的进步,其役用功能逐渐降低甚至消失。现代马产业主要以竞技、休闲娱乐及副产品加工为主,而驴产业则以皮、肉、乳及其生物制品的开发利用为主。马经济性状主要包括体型、毛色、竞赛能力、疾病、极端环境适应能力等,在驴上更关注生长、皮用和泌乳等性状。随着基因组学和生物信息学的发展,马、驴主要经济性状相关基因的发掘更为有效和精准：如与马体重、体尺相关的基因被定位于LCORL/NCAPG基因区域;MSTN基因与骨骼肌的发育相关,进而影响马竞赛性能;与设特兰矮马、德保矮马矮小性状相关的主要基因分别为HMGA2和TBX3基因;ACAN基因突变会导致设特兰矮马侏儒;DMRT3基因突变影响马的步态特征;KIT基因与白斑毛表型相关,MC1R基因是控制栗色毛的主要基因,ASIP基因与黑色毛相关;EDNRB基因突变会导致致死白色马驹综合征;EPAS1基因和线粒体NADH6基因在高原适应性进化中起重要作用。作者对马、驴主要经济性状相关功能基因的研究进展进行综述,并对功能基因组学研究进行展望,以期为今后开展马、驴分子遗传育种研究提供借鉴与参考。     

Anaesthesia and analgesia of the donkey and the mule

The number of donkeys and mules throughout the world is stable, and awareness of their use and concern for welfare, pain recognition and treatment are receiving increasing veterinary interest. Therefore, accurate information about anaesthesia and analgesia in donkeys and mules is important to ever more equine practitioners. Since donkeys are physiologically and pharmacologically different from horses, knowledge on species specific aspects of anaesthesia and analgesia are very important. Mules combine elements from both donkey and horse backgrounds, leading to great diversity in size, temperament and body type. Physiologically, they seem to resemble horses more than donkeys. This review highlights the current knowledge on various anaesthetic and analgesic approaches in donkeys and mules. There is still much information that is not available about donkeys; in many circumstances, the clinician must use available equine information to treat the patient, while monitoring carefully to observe for differences in response to therapy compared to the horse.     

Improving working donkey (Equus asinus) welfare and management in Mali,West Africa

Working conditions for cart donkeys in West Africa are often harsh. In collaboration with the Society for the Protection of Animals Abroad, we conducted 3 studies and a welfare assessment. In the first study, we compared behavioral and physiological measures of donkeys (n = 10) driven in 2 standard Malian ways (1 = halter and reins, 2 = no halter and with a stick). In a second study, we assessed pressure associated with harness and cart quality. Pressure was measured according to several different parameters, including type of harness (satisfactory or unsatisfactory), type of cart (satisfactory or unsatisfactory), and weight (no weight or 200 kg of weight). Because education likely plays an important role in enhancing working equid welfare, we conducted a third study aimed at educating paraprofessionals about donkey husbandry (n = 82). We also conducted a welfare assessment on a donkey population in Segou, Mali (n = 54). Among training methods, no significant difference was found in either heart rate variability or behavior. A significant difference in back/wither pressure (P < 0.05) was found for the following parameters: harness type (P = 0.02) and cart with weight (P = 0.009). The welfare assessment examined how body condition scores, age, number of lesions, scarring, lameness, behavior parameters, and dehydration were related. The results indicated a significant effect between body condition score and hydration, that is, donkeys with lower body conditions were often less hydrated (P = 0.01). The relationship of body condition was significant when comparing the behavioral response with the ear test (P = 0.03). Finally, educational workshops were conducted at 2 schools, one in Segou (n = 54 students) and one in Bamako (n = 28 students), to measure donkey management knowledge before and after a husbandry education seminar and practical demonstration were conducted. The average test scores for pre- and post-tests numerically increased at both schools. However, the increase in test scores was not significant (Segou P = 0.15 and Bamako P = 0.06). This study provides additional methods to professionals and paraprofessionals on alternative methods for training, harnessing, and working donkeys in developing parts of the world.     

Validation of a competitive enzyme-linked immunosorbent assay for diagnosing Babesia equi infections of Moroccan origin and its use in determining the seroprevalence of B. equi in Morocco.

A highly specific and sensitive competitive enzyme-linked immunosorbent assay for detection of specific antibody to Babesia equi in serum from equids was validated for use in Morocco. The assay is based on the specific inhibition of binding of a monoclonal antibody to a conserved epitope within a recombinant parasite peptide by serum from infected animals. The assay was compared to an established indirect immunofluorescence assay, with a concordance of 91%. The assay was used to determine seroprevalence for B. equi infections in donkeys and horses throughout Morocco. A total of 578 sera (163 horses and 415 donkeys) from 6 locations representing different bioclimatic regions were assayed. An analysis of variance, indicated no significant effect of location; however, donkeys were significantly more likely than horses to be seropositive. Management conditions contribute to greater tick infestations and thus Babesia exposure in donkeys than in horses.     

Coagulation profiles of healthy Andalusian donkeys are different than those of healthy horses

Background: Coagulation disorders are frequently diagnosed, especially in hospitalized equidae, and result in increased morbidity and mortality. However, hemostatic reference intervals have not been established for donkeys yet. Objectives: To determine whether the most common coagulation parameters used in equine practice are different between healthy donkeys and horses. Animals: Thirty‐eight healthy donkeys and 29 healthy horses. Methods: Blood samples were collected to assess both coagulation and fibrinolytic systems by determination of platelet count, fibrinogen concentration, clotting times (prothrombin time [PT] and activated partial thromboplastin time [aPTT]), fibrin degradation products (FDP) and D‐Dimer concentrations. Results: PT and aPTT in donkeys were significantly (P < .05) shorter than those of horses. In contrast, FDP and D‐Dimer concentrations were significantly (P < .05) higher in donkeys than in horses. Conclusions and Clinical Importance: The coagulation parameters most commonly determined in equine practice are different in donkeys compared with horses. Thus, the use of normal reference ranges reported previously for healthy horses in donkeys might lead to a misdiagnosis of coagulopathy in healthy donkeys, and unnecessary treatments in sick donkeys. This is the first report of normal coagulation profile results in donkeys, and further studies are warranted to elucidate the physiological mechanisms of the differences observed between donkeys and horses.