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.     

Efficacy of intramammary treatment with procaine penicillin G vs. procaine penicillin G plus neomycin in bovine clinical mastitis caused by penicillin-susceptible,gram-positive bacteria--a double blind field study

The efficacy of intramammary treatments containing procaine penicillin G alone (treatment A) or a combination of procaine penicillin G and neomycin (treatment B) was compared in treating clinical bovine mastitis caused by gram-positive bacteria susceptible in vitro to penicillin G. Both treatments were supplemented with a single intramuscular injection of procaine penicillin G on the first day of treatment. The study was carried out using a double blind design on commercial dairy farms in Southern Finland. A total of 56 quarters were treated with treatment A and 61 with treatment B. The cure rates for both treatments were equal, which suggests that the use of the penicillin G-aminoglycoside combination does not increase the efficacy of the treatment over that achieved by using penicillin G alone in bovine clinical mastitis caused by penicillin-susceptible, gram-positive bacteria.     

Effects of supplement type and selenium source on measures of growth and selenium status in yearling beef steers

Sugarcane molasses is a widely used animal feed by-product, but is concentrated in S (approximately 1%, DM basis) and has been shown to reduce the Cu status of cattle. Dietary S may also antagonize Se; therefore, two 90-d studies were conducted with forage-fed, yearling steers (12 pens; 2 steers/pen for each study) to investigate the impact of molasses supplementation on measures of Se status. In Exp. 1, steers were assigned isonitrogenous supplements with equivalent amounts of TDN from 2 sources (molasses or corn). Supplemental Se was provided (3.0 mg of Se/d; Na selenite) to both treatments. After 90 d of supplementation, steers provided corn diets had greater (P = 0.02) liver Se concentrations and tended (P = 0.07) to have greater ADG compared with steers supplemented with molasses. Irrespective of treatment (P >/= 0.54), plasma Se concentrations decreased (P < 0.001) and plasma glutathione peroxidase activity increased (P < 0.001) from d 0 to 90. In Exp. 2, sources of supplemental Se (2.5 mg/ d), fed within molasses supplements, were compared. Treatments included 1) Na selenite, 2) Se-yeast (Sel-Plex, Alltech, Nicholasville, KY), or 3) no Se (control). Cattle provided supplemental Se, irrespective of source, had greater (P 相似文献   

Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows

This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (±SD) were: C _max, 5.5 ± 2.6 μg/mL; T _max, 0.75 ± 0.27 h; AUC _0-∞, 10.8 ± 4.9 μg·h/mL; MRT , 2.2 ± 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows.     

Ceftiofur distribution in plasma and tissues following subcutaneously administration in ducks

A study was performed to determine the residues in blood and edible tissues of healthy ducks (25 days old, mean body weight 1.0+/-0.13 kg) after subcutaneous administration of ceftiofur sodium at a dose rate of 2 mg/kg body weight (Group I) and 4 mg/kg body weight (Group II). Blood, muscle, liver, kidney, and fat samples were collected from all of ducks on the 1st, 2nd, 3rd, 4th, and 5th day after treatment of drug, and ceftiofur was analyzed with a high-performance liquid chromatography (HPLC) assay with results reported as ceftiofur-free acid equivalent (CFAE). To study the spiked recovery, blank plasma and tissues were spiked with two different concentrations of ceftiofur sodium (0.1, 0.5 microg/g). Average recovery values for all samples ranged from 70.3 to 87.3%. In the group I, desfuroylceftiofur acetamide (DCA) was not detected in all of plasma, muscle, liver, and fat tissues on the 1st day after treatment. But, kidney samples on the 1st day were detected DCA (0.059+/-0.01 microg CFAE/g tissue). On the 2nd day of post-treatment, the concentrations of DCA in all tissues were lower than the detection limit, 0.05 microg CFAE /g tissue. In the group II on the 1st day after treatment, the concentration of DCA was 0.124+/-0.06 microg CFAE/g tissue, 0.103+/-0.03 microg CFAE/g tissue, and 0.071+/-0.010 microg CFAE/g tissue in plasma, kidney, and muscle samples, respectively. On the 2nd day after treatment of ceftiofur, the concentrations of DCA in all tissues were lower than 0.05 microg CFAE/g tissue. According to our results, the concentrations of DCA on the 1st day after treatment with 2 mg/kg body weight were below 0.05 microg CFAE/g tissue equivalent in all tissues except for kidney. On the 2nd day after administration at the dose of 4 mg/kg body weight, no DCA was also detected in all of the tissues although DCA was detected in all samples on the 1st day.     

Influence of sodium bicarbonate and magnesium oxide on digestion and metabolism in yearling beef steers abruptly changed from high forage to high energy diets

Eight rumen-cannulated steers (initial wt 330kg) were adapted to a mixed alfalfa-grass hay diet for 30 d and abruptly changed to complete mixed diets of corn silage, snapped ear corn and a corn-based supplement to determine the effects of buffers on diet adaptation, digestion and ruminal metabolism. The diets contained: 1) no buffer, 2) .5% magnesium oxide (MgO), 3) 1.0% sodium bicarbonate (NaHCO3) and 4) .5% MgO and 1.0% NaHCO3, as a percentage of diet dry matter (DM). Digestion, metabolism and ruminal characteristics were measured in each of 2 wk immediately after the diet change. The animals were then adapted to the mixed alfalfa-grass hay diet, re-randomized and assigned to the four diets, thus four steers consumed each diet. Intakes and digestibilities of DM were generally greater for the diets containing buffers. The most notable differences were a greater DM intake with added NaHCO3 and an improved DM digestibility with added MgO. The higher DM digestibility with MgO was apparently related to improved neutral detergent fiber (NDF) and starch digestion. Fecal pH was significantly increased with MgO addition. Because of the greater intake and digestibilities, the amount of DM, NDF, and starch digested tended to be greater for the buffered diets. There were no diet X week interactions for intake and digestibilities, thus the responses observed existed during both wk 1 and 2 after the change in diets. In general, intake and digestibilities were greater in wk 2 than in wk 1 for all diets.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of clindamycin HCl administered intravenously, intramuscularly and subcutaneously to dogs

A buffered aqueous solution of clindamycin Hcl (200 mg/mL) was injected intravenously (i.v.) intramuscularly (i.m.) and subcutaneously (s.c.) in a non-randomized, partial cross-over trial involving six male and six female dogs. Blood samples were collected at conventional, predetermined time periods and serum drug concentrations were determined by microbiological assay. Dogs were observed clinically for signs of pain, and activity of serum creatine phosphokinase (CPK) was monitored after i.m. dosing. The i.v. data from five of the dogs best fitted a two-compartment open-system pharmacokinetic model whereas a non-compartment model was most suitable for analysis of the data from the remaining seven dogs. The mean i.v. elimination half-life (t1/2 beta) and the mean residence time (MRT) were 124 and 143 min, respectively. The mean volume of distribution at steady state (Vss) was 0.86 L/kg. Little pain was recorded upon i.m. injection; mean peak serum drug concentration (Cmax) was 4.4 micrograms/mL, the elimination half-life (t1/2el) was 247 min and the calculated bioavailability (F) was 115% of the i.v. dose. Serum CPK activity was elevated to 25-fold the pretreatment level in samples collected 4, 8 and 12 h after i.m. injection. Pain was not recorded after s.c. drug administration; the mean Cmax of 20.8 micrograms/mL was significantly greater than the corresponding value for the i.m. route, and F was 310%. The s.c. route appears to be superior to the i.m. route in terms of local tolerance and serum drug level; a 10 mg/kg SID treatment regimen is suggested for treatment of canine infections due to clindamycin sensitive bacteria.     

Effect of the injection site on the pharmacokinetics of procaine penicillin G in horses

The plasma penicillin concentrations were determined in 5 horses given an IV injection of sodium penicillin G; plasma penicillin concentrations were also determined in a crossover experiment, where animals were given procaine penicillin G subcutaneously at 1 site and IM at 4 sites. The mean penicillin plasma peak concentration and bioavailability were highest after the drug was injected in the neck and biceps musculature. Injections in the gluteal muscle and in the subcutaneous sites resulted in similar, but lower, more persistent penicillin plasma concentrations and a lower bioavailability than were obtained with injection in the neck and biceps musculature. The pharmacokinetic data obtained after penicillin was administered via the pectoral muscle route exhibited an intermediate position. Therapeutic implications of the routes of administration with respect to hemolytic streptococcal infections are discussed.     

地西泮在猪体内的血浆药动学及消除规律

苯二氮卓类药物(benzodiazepines,BZ)是镇静催眠药,兽医主要用于各种动物镇静、保定、基础麻醉、术前给药及癫痫的治疗等方面[1-2],畜牧生产中曾被用作猪抗运输应激[3]及奶牛抗热应激[4]的药物.近年来,随着畜牧养殖业的迅速发展,一些不法分子在经济利益的驱动下,擅自在畜禽饲养中添加使用.BZ在饲料中的滥用,将最终导致畜产品中药物的残留,从而严重影响人们的身体健康,威胁人们的生命安全.我国农业部2002年4月发布<食品动物禁用的兽药及其他化合物清单>中,明令禁止将此类药物以抗应激、提高饲料报酬、促进动物生长为目的在食用动物饲养过程中使用.     

Antibiotic residues in milk following bulbar subconjunctival injection of procaine penicillin G in dairy cows

OBJECTIVE: To determine whether, and at what time, penicillin enters milk at a concentration that is detectable following bulbar subconjunctival injection in lactating dairy cows. DESIGN: Randomized clinical trial. ANIMALS: 66 Holstein cows that were at least 2 weeks past calving and had not been treated with antibiotics in the preceding 30 days. PROCEDURE: Cows were randomly assigned to receive a treatment of 1 ml (300,000 units) procaine penicillin G by bulbar subconjunctival injection or remain untreated. Composite milk samples were collected immediately before treatment and 4, 10, 16, 22, 28, and 40 hours after treatment. Milk samples were tested by use of a commercial test for beta-lactam antibiotics. RESULTS: Among penicillin-treated cows, the first positive test results were observed 4 hours after treatment, and the last positive result was observed 22 hours after treatment. The percentages of positive test results before treatment and at 4, 10, 16, 22, 28, and 40 hours after treatment were 0, 9, 87, 42, 8, 0, and 0%, respectively. None of the untreated cows had positive test results for beta-lactam antibiotics at any sampling time. CONCLUSIONS AND CLINICAL RELEVANCE: Penicillin was detected in milk for up to 22 hours after a single subconjunctival injection of procaine penicillin G in cows. This result should be considered when recommending milk withholding periods following the administration of penicillin by this route in lactating dairy cows.     

Nitrogen and protein metabolism and metabolites in plasma and urine of beef steers treated with somatotropin

The objectives of this study were to determine the effects of daily injection of bovine somatotropin (bST) on the metabolism of N and 1-[14C]leucine and on hormone and metabolite concentrations in growing beef steers. Injection of bST increased N retention (P less than .05) primarily through decreased (P less than .10) urinary N excretion. Plasma concentration of somatotropin, insulin and glucose increased (P less than .01) and of urea-N (P less than .01) and alpha-amino-N (P less than .10) decreased with bST compared with excipient injection. Total leucine flux was not altered by treatment; however, the partition of flux was. Leucine oxidation decreased (P less than .05) and leucine used for protein synthesis (P less than .10) increased, with bST compared with excipient injection. During excipient injection, 10.3 g protein were synthesized for each gram crude protein deposited, whereas during bST injections only 6.4 g were required. The average maximum contribution of myofibrillar protein degradation to whole body protein degradation, calculated from excretion of 3-methylhistidine, was 16%. Although the ratio of protein deposition/protein synthesis was low for both excipient- and bST-injected steers, the incremental efficiency of protein deposition was 50%, reflecting a dilution of protein synthesis required for turnover and a proportionately greater increase in protein synthesis than protein degradation with bST injection. In growing beef steers, bST stimulated whole body protein synthesis and decreased leucine oxidation. The change in partition of leucine flux, but not of total flux (irreversible loss), demonstrates a chronic redirection in metabolism consistent with homeorhetic control. These data from steers injected with bST suggest mechanisms by which bST affects metabolism during normal growth.     

Bioavailability and disposition of sodium and procaine penicillin G (benzylpenicillin) administered orally with milk to calves

Eighteen 1-week-old Holstein calves were randomly assigned to one of three groups: (a) sodium penicillin G administered intravenously, (b) sodium penicillin G administered orally, or (c) procaine penicillin G administered orally. All calves were dosed with penicillin G at 4.0 mg/kg BW. At 5 weeks of age, the calves were dosed again. Blood samples were taken serially for 24 h after both dosings. Plasma was assayed for penicillin G by high performance liquid chromatography (HPLC). For i.v. administration, the area under the concentration-time curve (AUC), 7456 and 5508 ng/mL h, and systemic clearance, 0.54 and 0.73 L/kg h, were significantly different (P < 0.05) at 1 and 5 weeks of age, respectively. There were no significant differences between orally administered sodium and procaine penicillin G within the same age groups. Following oral (p.o.) administration, there were significant differences (P < 0.01) at 1 and 5 weeks of age in the AUC, 760 and 409 ng/mL h, terminal half-life, 2.1 and 1.6 h, time of maximum concentration (TMAX), 3.0 and 2.3 h, and maximum plasma concentration (CMAX), 85 and 58 ng/mL, respectively. Bioavailability was 10.2 and 7.4% at 1 and 5 weeks, respectively.     

Nonstructural carbohydrate supplementation of yearling heifers and range beef cows

A digestion study with 28 yearling heifers (428 +/- 9.9 kg; Exp. 1) and a 2-yr winter grazing trial with 60 crossbred cows (552 +/- 6.9 kg; Exp. 2) were used to determine the effects of level of nonstructural carbohydrate (NSC) supplementation on intake and digestibility of low-quality forage. Treatments were as follows: 1) control, no supplement; 2) 0.32 kg of NSC (1.8 kg/d of soybean hulls and soybean meal; DM basis); 3) 0.64 kg of NSC (1.7 kg/d of wheat middlings; DM basis); and 4) 0.96 kg of NSC (1.7 kg/d of barley and soybean meal; DM basis). Supplements provided 0.34 kg of CP/d and 5.1 Mcal of ME/d. In Exp. 1, heifers were individually fed hay (5.5% CP, DM basis) and their respective supplements in Calan gates for 28 d. Data were analyzed as a completely randomized design. In Exp. 2, cows were individually fed supplement on alternate days, and grazed a single rangeland pasture stocked at 1.8 ha/ animal unit month. Two ruminally cannulated cows were used per treatment to obtain forage extrusa and to measure in situ DM disappearance (DMD) and carboxymethylcellulase (CMCase) activity of particle-associated ruminal microbes. Data were analyzed as a completely randomized design with the effects of treatment, year, and their interaction. In both experiments, Cr2O3 boluses were used to determine fecal output, individual animal was the experimental unit, and contrasts were used to test linear and quadratic effects of NSC level and control vs. supplemented treatments. In Exp. 1, hay and diet DM, NDF, and CP intakes and digestibilities were increased (P < 0.01) by NSC supplementation compared with the control. In Exp. 2, 72-h in situ DMD and CMCase were decreased linearly (P < 0.08) with increasing NSC supplementation. Intake of forage DM, NDF, and CP was decreased linearly (P < 0.01) with increasing NSC supplementation during both years. Supplementation with NSC decreased (P = 0.01) cow BW loss compared with the control in yr 1, whereas in yr 2, cow BW loss was linearly increased (P = 0.03) by increasing NSC supplementation. Supplements containing NSC improved forage digestion and intake when heifers consumed forage deficient in CP relative to energy (digestible OM:CP > 7), but decreased forage digestion and intake when cows grazed forage with adequate CP relative to energy (digestible OM:CP < 7). Forage and supplement digestible OM:CP seemed to be superior predictors of response to supplementation with NSC compared with forage CP levels alone.