甲砜霉素在感染多杀性巴氏杆菌鸡体内的药物动力学

30只健康杂交肉鸡随机分成3组,每组10只,雌雄各半,分别进行健康鸡静脉注射、健康和巴氏杆菌感染鸡口服给药的药动学研究。静注和口服的给药剂量按体质量分别为15mg/kg和30mg/kg。以反相HPLC测定血浆中甲砜霉素的质量浓度,药物浓度-时间数据用3P97药动学程序软件处理。健康鸡单剂量静注给药后,血药浓度-时间数据符合无吸收二室开放模型,其主要动力学参数分别为:V(c)为(0.58±0.09)L/kg,t1/2α(0.11±0.03)h,t1/2β(0.95±0.18)h,AUC为(11.99±0.90)mg/(L.h),CL(s)为(1.26±0.10)L/(kg.h)。健康鸡和巴氏杆菌感染鸡单剂量口服给药血药浓度-时间数据均符合一级吸收一室开放模型。健康鸡口服给药的主要动力学参数分别为:Lagtime(0.04±0.02)h,t1/2ka(0.16±0.08)h,t1/2ke(1.64±0.22)h,T(peak)(0.57±0.18)h,C(max)(6.34±0.56)mg/L,AUC为(19.02±1.48)mg/(L.h),F为79.32%。巴氏杆菌感染鸡口服给药的主要动力学参数分别为:Lagtime(0.07±0.02)h,t1/2ka(0.54±0.26)h,t1/2ke(1.74±0.27)h,T(peak)(1.31±0.39)h,C(max)(5.28±0.73)mg/L,AUC为(21.75±1.03)mg/(L.h),F90.70%。与健康鸡相比,甲砜霉素在感染鸡的t1/2(ka)、T(peak)和Lag-time显著延长(P0.05或P0.01),且比健康鸡具有更高的生物利用度。但甲砜霉素在巴氏杆菌感染鸡体内的消除速度未受影响。     

普鲁卡因青霉素－硫酸双氢链霉素混悬剂对猪链球菌病的临床药效观察

本研究报道了普鲁卡因青霉素－硫酸双氢链霉素混悬剂对试验性感染猪链球菌病的临床药效学。以试管2倍稀释法测得兰氏C群类马链球菌对青霉素、恩诺沙星的最小抑菌浓度(MIC)分别是0.0313、0.5 mg/L。肌注给药对猪链球菌病的试验性治疗结果表明,低、中、高剂量普鲁卡因青霉素－硫酸双氢链霉素混悬剂组(0.05、0.1、0.2 mL/kg体重,每毫升混悬剂含普鲁卡因青霉素、硫酸双氢链霉素200000 IU和250000 IU)及恩诺沙星组(2.5 mg/kg体重)用药3 d,对猪链球菌病的治愈率分别是60%、80%、90%及60%,而链球菌感染对照的死亡率为70%。     

头孢喹肟在猪体内的药动学及生物利用度

10头健康杂种猪,随机交叉设计试验,头孢喹肟按1 mg/kg的剂量分别进行耳缘静脉和颈部肌肉单点注射给药,给药间隔时间为1周.采用反相高效液相色谱法测定血清中头孢喹肟的药物浓度,用药代动力学程序软件3P97处理血清中药物浓度-时间数据.结果表明,静脉注射给药后,猪血清中头孢喹肟的药时数据符合二室开放模型,其主要药动学参数为:t1,2α为0.16 h,t1/2β为1.34 h,V(c)为0.24 L·kg1,cl‘.)为0.26 L·kg-1·h-1,AUC为3.97 mg·L-1·h;颈部肌肉单点注射给药后,猪血清中头孢喹肟的药时数据符合一级吸收二室模型,其主要药动学参数为:t1/2ka为0.08 h,t1/2α为0.84 h,t1/2β日为2.76 h,t(max)为0.32 h,C(max)为1.80 mg·L-1Cl(s)为0.25 L·kg-1·h-1,AUC为4.12 mg·L-1·h,F为102.37%.     

乳酸恩诺沙星可溶性粉在鸡体内的药动学研究

24只苏禽黄羽肉鸡随机分成2组,分别按10 mg/kg体重剂量静注和内服乳酸恩诺沙星。测定乳酸恩诺沙星在鸡体内的药动学参数和生物利用度。恩诺沙星血药浓度数据用3p87计算机软件处理。静注乳酸恩诺沙星后的血药浓度-时间数据符合二室开放模型,主要动力学参数:t1/2α(0.45±0.16)h,t1/2β(7.02±1.42)h,CL(s)(0.38±0.10)L/kg/h,AUC(23.69±5.56)(mg/L)×h。内服乳酸恩诺沙星的血药浓度时间数据,符合有吸收因素二室模型,主要动力学参数:t1/2ka(0.60±0.01)h,t1/2ke(8.25±1.73)h,tpeak(2.44±0.17)h,Cmax(1.44±0.30)mg/L,AUC(20.74±3.80)(mg/L)×h,F 87.54%。结果表明,乳酸恩诺沙星可溶性粉在鸡体内具有吸收快、分布广、消除较慢以及内服生物利用度高的药动学特征。     

地克珠利在獭兔体内的药物动力学研究

选用10只体重为1.8±0.33kg的獭兔按10mg/kg体重单次经口灌服0.2%地克珠利预混剂后,于设定的时间点采血,乙腈提取血样,高效液相色谱法测定血药浓度,3P97药动学软件分析。结果表明,该药在兔体内吸收、分布和消除均较快,半衰期(t1/2ka,t1/2α,t1/2β)分别为0.51h、3.44h、8.8h,最大血药浓度(Cmax)为16.47μg/mL,达峰时间(Tmax)为1.75h,药时曲线下面积(AUC)为159.05μg·h/mL,平均滞留时间(MRT)为9.77h,房室分析表明,其药时数据符合一级吸收的二室模型。     

单诺沙星在雏鸡体内的药动学特征及生物利用度研究

以高效液相色谱法为定量手段研究了单诺沙星内服给药在雏鸡体内的药动学特征及生物利用度。 12 0只雏鸡静注或内服单诺沙星 (5mg/kg)后 ,血药浓度时间数据分别符合无吸收二室模型和一级吸收二室模型。静注给药的主要动力学参数为t1/ 2α0 .34h ,t1/ 2 β为 7.3184h ,VB 为 16 .0 6 31L/kg ,AUC为 3.2 872mg/L·h ,Tcp为 2 5 .0 1h。内服给药的主要动力学参数如下 :t1/ 2ka为 0 .2 42 8h ,t1/ 2α为 0 .8917h ,t1/ 2 β为 8.7936h ,Tp 为 0 .9377h ,Cmax为 0 .5 487μg/mL ,AUC为3 .0 5 2 3mg/L·h ,Tcp为 31.115h。内服生物利用度为 92 .85 %。     

20%吡喹酮注射剂在水牛体内的药代动力学研究

4头成年健康水牛采用随机交叉实验设计,分别进行吡喹酮注射剂肌注和吡喹酮片内服给药的药动学试验.吡喹酮注射剂按10 mg/kg的剂量单次肌注,吡喹酮片按20 mg/kg的剂量单次内服给药.采用高效液相色谱法测定血浆中吡喹酮的质量浓度,方法最低检测限和定量限分别为0.01 mg/L和0.062 5 mg/L.吡喹酮注射剂单剂量肌注给药,血药浓度-时间数据符合一级吸收一室开放模型,其主要动力学参数分别为:t1/2(ka)(0.45±0.029)h,t1/2(ke)(5.04±0.1 0)h,T(peak)(1.72±0.029)h,C(max)(0.87±0.006)mg/L,V(c)(8.58±0.010)L/kg,AUC(7.99±0.005)mg·L-1·h-1.吡喹酮片单剂量口服给药血药浓度-时间数据符合有吸收-室开放模型,其主要动力学参数分别为:Lagtime(0.13±0.010)h,t1/2(ka)(0.76±0.11)h,t1/2(ke),(1.31±0.076)h,T(peak)(3.84±0.026)h,C(max)(0.51±0.006)mg/L,V(c)(26.07±1.221)L/kg,AUC(7.99±0.005)mg·L-11·h-1.肌注相对生物利用度为(232±12.9)%.研究结果表明,20%吡喹酮注射剂肌注给药吸收迅速且完全,具有较高的生物利用度;吡喹酮吸收后在体内广泛分布.     

健康仔猪单剂量内服左旋氧氟沙星的药动学研究

以20mg/kg剂量内服进行左旋氧氟沙星的辩证药动学研究。高效液相色谱法测定血浆药物浓度、3P97药代动力学程序处理药时数据。健康组药时数据符合一级吸收一室模型,其主要药动学参数为:吸收半衰期t1/2ka(0.42±0.08)h,消除半衰期t1/2ke(7.62±0.38)h,达峰时间tmax(1.85±0.25)h,峰浓度Cmax(6.99±0.92)mg/L,药时曲线下面积AUC(90.7±10.07)mg/L·h,生物相表观分布容积VF(s)(2.45±0.28)L/kg,平均滞留时间MRT(11.92±0.94)h。     

单诺沙星在支原体一大肠杆菌感染鸡体内的药动学与生物利用度的研究

以高效液相色谱法为定量手段研究了单诺沙星内服给药在支原体与大肠杆菌合并感染鸡体内的药动学特征及生物利用度。 12 0只合并感染雏鸡静注或内服单诺沙星 (5mg/kg)后 ,血药浓度时间数据分别符合无吸收二室模型和一级吸收二室模型。静注给药的主要动力学参数为t1/ 2α0 .5 0 34h,t1/ 2 β为 6 .8485h,VB 为 12 .16 0 3L/kg,AUC为 40 6 33mg/L·h ,Tcp为 2 5 .2 43h。内服给药的主要动力学参数如下 :t1/ 2ka为 0 .3182h ,t1/ 2α为 1.5 5 0 2h ,t1/ 2 β为 12 .6 2 0 0h ,Tp 为 1.110 7h ,Cmax为 0 .5 10 6 μg/mL ,AUC为 3.6 6 2mg/Lh ,Tcp为 39.18h。内服生物利用度为 90 .0 8%。     

恩诺沙星及其活性代谢物在传染性鼻炎鸡体的药动学

为建立鸡传染性鼻炎的药动学模型,研究了恩诺沙星及其活性代谢物在传染性鼻炎鸡体内的药动学特征.用反向高效液相色谱法测定血浆中的药物浓度,所得恩诺沙星的ci-ti数据用MCPKP程序处理,代谢物环丙沙星的ci-ti数据用代谢物动力学方法处理.结果表明,鸡静注恩诺沙星后的ci-ti数据符合二室开放模型,其主要动力学参数如下:t1/2α(0.25±0.04) h、t1/2β(5.46±0.71) h、Vd(4.21±1.09) L/kg、CLB(0.54±0.11) L/(kg.h)、AUC(19.68±3.50) mg/(L.h).鸡内服恩诺沙星的ci-ti数据,符合有吸收因素二室模型,其主要动力学参数如下:t1/2ka(0.44±0.11) h、t1/2α(1.17±0.40) h、t1/2β(9.24±2.07) h、AUC(12.23±3.68) mg/(L.h)、tmax(1.50±0.29) h、Cmax(1.34±0.44) mg/L、F 62.26%.恩诺沙星在感染鸡体内的动力学特征是吸收迅速、分布广泛、消除缓慢;感染鸡静注与内服恩诺沙星后,代谢物环丙沙星的动力学特征是生成及消除缓慢、分布广泛.鸡传染性鼻炎可使恩诺沙星内服的生物利用度下降,但对恩诺沙星的分布、消除及代谢物的动力学过程无显著影响.     

Benzathine Penicillin G and Procaine Penicillin G in Piglets: Comparison of Intramuscular and Subcutaneous Injection

The disposition of penicillin G in piglets is described after intramuscular or subcutaneous injection of depot preparations. The piglets were injected with 33 000 IU/kg or 100 000 IU/kg benzathine + procaine penicillin G intramuscularly or subcutaneously, or 100 000 IU/kg procaine penicillin G intramuscularly or subcutaneously. Intramuscular injection of benzathine + procaine penicillin resulted in higher maximum concentration in plasma (C_max) than did subcutaneous injection. The mean residence time (MRT) of penicillin G was longer when the drugs were injected subcutaneously rather than intramuscularly. The plasma concentration versus time profiles of the subcutaneous injections of benzathine + procaine penicillin revealed secondary peaks, possibly reflecting a certain degree of inflammation at the injection site.     

Distribution of penicillins into subcutaneous tissue chambers in ponies

The distribution of penicillins into a tissue chamber implanted subcutaneously in ponies was studied. Ampicillin sodium (equivalent to 15 mg/kg ampicillin) was administered intravenously. Pivampicillin, a prodrug of ampicillin, was administered by nasogastric tube to fed ponies at a dose of 19.9 mg/kg (equivalent to 15 mg/kg ampicillin). Procaine penicillin G was administered intramuscularly at a dose of 12 mg/kg (equivalent to 12 000 IU/kg). Six ponies were used for each medication. Antibiotic concentrations in plasma and tissue chamber fluid (TCF) were measured for 24 h after administration. Mean peak concentrations of ampicillin in TCF were 7.3 μg/mL, reached at 1.7 h, and 1.3 μg/mL, reached at 2.7 h, after administration of ampicillin sodium and pivampicillin respectively. The mean peak concentration of penicillin G of 0.3 μg/mL was reached 12.3 h after administration of procaine penicillin G. Concentrations in TCF remained above the minimum inhibitory concentration of Streptococcus zooepidemicus for the proposed dosing intervals of 8, 12 and 24 h for ampicillin sodium, pivampicillin and procaine penicillin G respectively.     

Depletion of intramuscularly and subcutaneously injected procaine penicillin G from tissues and plasma of yearling beef steers.

Withdrawal periods required when doses of 24,000 IU and 66,000 IU of procaine penicillin G/kg body weight were administered to yearling beef steers by intramuscular injection daily for five consecutive days were investigated. These dosages are in excess of product label recommendations, but are in the range of procaine penicillin G dosages that have been administered for the treatment of some feedlot bacterial diseases. The approved dose in Canada is 7,500 IU/kg body weight intramuscularly, once daily, with a withdrawal period of five days. Based on the tissue residue data from this study, the appropriate withdrawal period is ten days for the 24,000 IU/kg body weight dose and 21 days for the 66,000 IU/kg body weight dose when administered intramuscularly to yearling beef steers. In a related study, 18 yearling beef steers received 66,000 IU of procaine penicillin G/kg body weight administered by subcutaneous injection, an extra-label treatment in terms of both dose and route of administration, typical of current practice in some circumstances. Deposits of the drug were visible at subcutaneous injection sites up to ten days after injection, with more inflammation and hemorrhage observed than for intramuscular injections of the same dose. These results suggest that procaine penicillin G should not be administered subcutaneously at high doses; and therefore a withdrawal period was not established for subcutaneous injection.     

Evaluation of route and frequency of administration of three antimicrobial drugs in cattle

This study in six cows compared serum concentrations of trimethoprim and sulphadoxine (16 mg/kg body weight (BW)) after once daily and twice daily administration, and of procaine penicillin G (20,000 IU/kg BW) after subcutaneous (SQ) and intramuscular (IM) administration, and evaluated postmortem tissue concentrations of penicillin following SQ treatment. Trimethoprim and penicillin were measured microbiologically, and sulphadoxine colorimetrically. Using minimum inhibitory concentrations (MIC), trimethoprim reached serum concentrations above 0.5 μg/mL from 15 minutes to 120 minutes, and sulphadoxine exceeded 9.5 μg/mL from 10 minutes to 12 hours, after administration. At 24 hours after treatment, both had declined to below the MIC of most organisms. A second treatment at 12 hours maintained concentrations of sulphadoxine above 9.5 μg/mL for a further 24 hours. For penicillin administered IM and SQ, concentrations that peaked at 0.88 μg/mL would inhibit most common grampositive bacteria for the entire 24 hour period and fastidious gram-negative organisms from 90 minutes to 12 hours after SQ treatment, but for virtually the entire period after IM administration. Mean ± SD concentrations (μg/mL) of penicillin at euthanasia, five days after the last SQ administration, were 1.15 ± 1.27 (injection site), 1.00 ± 0.80 (liver), 0.90 ± 0.58 (renal cortex), 0,58 ± 0.17 (renal medulla), 0.13 ± 0.11 (diaphragm), 0.10 ± 0.08 (gluteal muscle), and 0.06 ± 0.04 (fat). Therefore, except for the most sensitive organisms, twice daily injection of trimethoprim/sulphadoxine (16 mg/kg BW) may be required. Penicillin G administered SQ at 20,000 IU/kg BW should provide effective serum levels for as long as IM administration against gram-positive organisms, but for only about half as long against gram-negative bacteria. The label withdrawal time of five days cannot be used when penicillin is given SQ at 20,000 IU/kg BW for three days.     

The role of procaine in adverse reactions to procaine penicillin in horses

Procaine penicillin is a commonly used antibiotic in equine medicine but its use is associated with a substantial incidence of adverse reactions. Soluble procaine concentrations were determined by HPLC in several commercially available procaine penicillin preparations, including some that were involved in adverse reactions. The mean (+/- SEM) soluble procaine concentrations in the veterinary preparations was 20.18 +/- 5.07 mg/ml, which was higher than the concentration in the only procaine penicillin preparation for use in humans in Australia of 7.3 mg/ml. Heating the veterinary procaine penicillin preparations to 50 degrees C for 1 day led to a significant (P less than 0.01) increase in the amount of soluble procaine. Heating to 50 degrees C for 7 days also produced a significant (P less than 0.02) increase. Soluble procaine tended to return to baseline concentrations when veterinary procaine penicillin preparations were heated to 50 degrees C for 2 days then stored for 7 days at room temperature. Administration of procaine HCl intravenously (IV) at 2, 5, and 10 mg/kg produced behavioural, locomotor and vascular reactions, which were clinically similar to those reported in adverse reactions to procaine penicillin. The more severe reactions occurred at higher doses, although different horses responded variably at the same dose. Some adverse reactions lead to recumbency but none were fatal. The blood procaine concentrations 1 min after IV administration averaged 19.0 +/- 12.6 and 25.3 +/- 16 micrograms/ml at 2.5 mg/kg and 5 mg/kg, respectively. Ten min after administration, blood procaine concentrations were significantly higher (P less than 0.001) in the 5 mg/kg group than in the 2.5 mg/kg group. Intramuscular (IM) procaine HCl at 5 mg/kg produced significantly lower (P less than 0.001) blood concentrations than similar IV doses, and, in contrast to the IV doses, the amount of procaine in the blood was significantly higher 5 and 10 min after administration than it was after 1 min. Mild excitatory reactions in 4/5 horses were noted 5 to 10 min after IM administration. Administration of diazepam 20 s before procaine HCl prevented the excitatory adverse reaction in 2/2 horses, but administration after the procaine did not influence the outcome.     

Clinical efficacy of trimethoprim/sulfadiazine and procaine penicillin G in a Streptococcus equi subsp. zooepidemicus infection model in ponies

Tissue chambers, implanted subcutaneously on both sides of the neck in eight ponies, were inoculated with Streptococcus equi subsp. zooepidemicus in order to compare the clinical efficacy of trimethoprim/sulfadiazine (TMP/SDZ) and penicillin G treatment in a purulent infection. The TMP/SDZ treatment consisted of one intravenous (i.v.) injection of 5 mg/kg TMP and 25 mg/kg SDZ and the same dose of TMP/SDZ per os (p.o.), both given 20 h after inoculation. The oral dose was then repeated every 12 h for 21 days. The penicillin treatment consisted of one i.v. injection of 20 000 IU/kg sodium penicillin G and intramuscular (i.m.) injection of 20 000 IU/kg procaine penicillin G, both given 20 h after infection. The i.m. dose was then repeated every 24 h for 21 days. Eight ponies, each with two tissue chambers, were used in a cross over design; in the first experiment the left tissue chamber (TC) was infected and in the second experiment the right. TMP/SDZ treatment resulted in a limited reduction of viable bacteria in the TC but did not eliminate the infection, resulting in abscessation in 10-42 days in all eight ponies. However, penicillin treatment eliminated the streptococci in seven of eight ponies, and only one pony suffered abscessation on day 10. This constitutes a significantly better efficacy of the penicillin treatment in this model. The most probable cause of the failure of TMP/SDZ to eliminate the streptococci is inhibition of the action of TMP/SDZ in the purulent TCF. Therefore, TMP/SDZ should not be used to treat purulent infections in secluded sites in horses.     

Clinical efficacy of ampicillin, pivampicillin and procaine penicillin G in a soft tissue infection model in ponies

Tissue chambers, implanted subcutaneously in ponies, were inoculated with Streptococcus zooepidemicus. The animals received either no antibiotics or one of the following treatments: pivampicillin per os (19.9 mg/kg, equivalent to 15 mg/kg ampicillin, every 12 h) for 7 or 21 days (7 and 5 ponies, respectively), procaine penicillin G intramuscularly (12 mg/kg = 12,000 IU/kg, every 24 h) for 7 days (7 ponies), or ampicillin sodium intravenously (equivalent to 15 mg/kg ampicillin, every 8 h) for 1 day (5 ponies). Only intravenous administration was started before infection (prophylactically), the other treatments were started 20 h after infection (curatively). A total of 7 ponies received no antibiotics. In untreated controls, the infection led to abscessation of the tissue chamber in 4 to 10 days. Curative treatment with either pivampicillin or procaine penicillin G for 7 days resulted in a reduction of viable bacteria in the tissue chamber but did not eliminate the infection, resulting in abscessation in 5 to 14 days. However, administration of pivampicillin for 21 days eliminated the streptococci in five out of five ponies and prophylactic administration of ampicillin was successful in three out of five ponies.     

Pharmacokinetics of penicillin G procaine versus penicillin G potassium and procaine hydrochloride in horses

OBJECTIVE: To compare the pharmacokinetics of penicillin G and procaine in racehorses following i.m. administration of penicillin G procaine (PGP) with pharmacokinetics following i.m. administration of penicillin G potassium and procaine hydrochloride (PH). ANIMALS: 6 healthy adult mares. PROCEDURE: Horses were treated with PGP (22,000 units of penicillin G/kg of body weight, i.m.) and with penicillin G potassium (22,000 U/kg, i.m.) and PH (1.55 mg/kg, i.m.). A minimum of 3 weeks was allowed to elapse between drug treatments. Plasma and urine penicillin G and procaine concentrations were measured by use of high-pressure liquid chromatography. RESULTS: Median elimination phase half-lives of penicillin G were 24.7 and 12.9 hours, respectively, after administration of PGP and penicillin G potassium. Plasma penicillin G concentration 24 hours after administration of penicillin G potassium and PH was not significantly different from concentration 24 hours after administration of PGP. Median elimination phase half-life of procaine following administration of PGP (15.6 hours) was significantly longer than value obtained after administration of penicillin G potassium and PH (1 hour). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that i.m. administration of penicillin G potassium will result in plasma penicillin G concentrations for 24 hours after drug administration comparable to those obtained with administration of PGP Clearance of procaine from plasma following administration of penicillin G potassium and PH was rapid, compared with clearance following administration of PGP.     

A study of the disposition of procaine penicillin G in feedlot steers following intramuscular and subcutaneous injection

The disposition of an aqueous suspension of procaine penicillin G (300 000 U/ mL) was studied in feedlot steers. Four groups of three steers were used. Steers in groups 1 and 2 received procaine penicillin G once daily for 5 days intramuscularly (i.m.) at a dose of 24 000 U/kg (group 1) or of 66 000 U/kg (group 2). The injection on the last day was administered in the gluteal muscle. Steers in group 3 (i.m. neck injection) and group 4 [subcutaneous (s.c.) injection] each received a single dose of procaine penicillin G at a dose of 66 000 U/kg. From every animal, after the last injection in groups 1 and 2 and following the single injection in groups 3 and 4, a series of blood samples was taken at fixed time intervals. The plasma from these samples was analysed for penicillin G by a high performance liquid chromatography (HPLC) assay in order to determine the disposition of penicillin. The maximum plasma concentration (C_max) and the area under the curve (AUC) were significantly different between groups 1 and 2, but we found no difference in the disappearance rate constant between these two groups. Group 4 single s.c. injections produced a lower mean C_max (1.85 ± 0.27 ng/mL) than the mean C_max (4.24 ± 1.08 μg/mL) produced in group 3 by i.m. injections into the neck muscle or the mean C_max (2.63 ± 0.27 μg/mL) produced in group 2 by i.m. injections into the gluteal muscle. However the mean C_max produced by i.m. injections into the neck muscles (group 3) was higher than the mean C_max produced by i.m. injections into the gluteal muscle (group 2). Additionally, the disappearance t_½, was longer (18.08 h) in group 4 following the s.c. injection and shorter (8.85 h) in group 3 following the i.m. neck injection, than the t_½ following administration of the same dose i.m. into the gluteal muscle (15.96 h) in group 2. In this study, when procaine penicillin G was injected into the gluteal muscle, doses of 66 000 U/kg were necessary to produce plasma concentrations that were above a minimum inhibitory concentration (MIC) for penicillin G of 1.0 μg/mL as compared to doses of 24 000 U/kg.     

Antibiotic prophylaxis of lower respiratory tract contamination in horses confined with head elevation for 24 or 48 hours

Objective To evaluate the administration of procaine penicillin prior to or during confinement with head elevation as a means of reducing the associated accumulation of inflammatory lower respiratory tract secretions and increased numbers of bacteria within the lower respiratory tract of confined horses. Design and Procedure Two experiments were conducted to evaluate the efficacy of different dose rates and dosing frequencies. In experiment A a single low dose (15,000 IU/kg) of procaine penicillin was administered to four horses immediately prior to confinement with head elevation for 48 hours. The systemic leucocyte response, gross and cytologic characteristics of transtracheal aspirate and bacterial numbers in lower respiratory tract samples were compared with corresponding samples from two horses confined with heads elevated but not given penicillin. The efficacy of higher dose rates (20,000 IU/kg and 40,000 IU/kg) given before and during confinement with heads elevated for 24 hours was evaluated in experiment B. Results Treatment with procaine penicillin had no effect on the systemic leucocyte response or on the accumulation of inflammatory lower respiratory tract secretions at any of the dosing schedules evaluated. The number of bacteria isolated from trans-tracheal samples was reduced at 12 hours for treated horses in experiment A and at 24 hours for experiment B. β-haemolytic Streptococcus spp were not isolated from treated horses in either experiment. Bacterial species isolated from treated horses were predominantly Pasteurella and/or Actinobacillus spp, however, members of the family Enterobacteriaceaé and a Staphylococcus sp were isolated from treated horses. One treated horse in experiment A developed clinically apparent pulmonary disease. Conclusions The prophylactic administration of penicillin before or during confinement did not reliably reduce bacterial numbers or prevent the accumulation of purulent lower respiratory tract secretions in horses confined with their heads elevated. Numbers of β-haemolytic Streptococcus spp were reduced following treatment, suggesting that the repeated administration of procaine penicillin may have some merit as part of a strategy to prevent transport-associated respiratory disease. However, methods directed at minimising the duration of confinement with head elevation, augmentation of the clearance of accumulated secretions and prompt identification of animals in which airway inflammation has extended to the pulmonary parenchyma remain the best ways of minimising transport-associated respiratory disease.