Pharmacokinetics of Cyadox and Its Major Metabolites in Swine After Intravenous and Oral Administration

Pharmacokinetics of cyadox (CYX) and its major metabolites in healthy swine was investigated in this paper. 1,4- Bisdesoxycyadox (BDCYX), cyadox-1-monoxide (CYX-1-O) and quinoxaline-2-carboxylic acid (QCA), three main metabolites of cyadox, were synthesized by College of Science, China Agricultural University. Cyadox (CYX) was administered to 8 healthy cross-bread swine intravenously (i.v.) and orally (p.o.) at a dosage of 1 mg kg-1 body weight and 40 mg kg-1 body weight respectively in a randomized crossover design test with 2-wk washout period. A sensitive high-performance liquid chromatography-tandem mass spectrometry (LC-ESI-MS/MS) method was developed for the determination of cyadox and its major metabolites in plasma. CYX and its major metabolites BDCYX, and CYX-1-O can be detected after intravenous administration of cyadox while CYX and its metabolites BDCYX, CYX-1-O and QCA can be detected after oral administration of CYX. Plasma concentration vs. time profiles of CYX and its major metabolites were analyzed by non-compartmental pharmacokinetic method. Following i.v. administration, the areas under the plasma concentration-time curve (AUC 0-∞ ) were (0.38±0.03) μg mL-1 h (CYX), (0.018±0.002) μg mL-1 h (BDCYX) and (0.17±0.02) μg mL-1 h (CYX-1-O), respectively. The terminal elimination half-lives (t 1/2λz ) were determined to be (0.93±0.07) h (CYX), (1.45±0.04) h (BDCYX), and (0.92±0.04) h (CYX-1-O), respectively. Steady-state distribution volume (Vss) of (2.14±0.11) L kg-1 and total body clearance (CL) of (2.84±0.19) L h-1 kg-1 were determined for CYX after i.v. dosing. The bioavailability (F) of CYX was 2.85% for oral administration. After single i.v. administration, peak plasma concentrations (C max ) of (1.08±0.06) μg mL-1 (CYX), (0.0068± 0.0004) μg mL-1 (BDCYX) and (0.25±0.03) μg mL-1 (CYX-1-O) were observed at T max of 0.033 h (CYX), 1 h (BDCYX) and 0.033 h (CYX-1-O), respectively. The main pharmacokinetic parameters after p.o. administration were as follows: AUC 0-∞ were (0.42±0.04) μg mL-1 h (CYX), (1.38±0.14) μg mL-1 h (BDCYX), (0.59±0.02) μg mL-1 h (CYX-1-O) and (1.48±0.09) μg mL-1 h (QCA), respectively. t 1/2λz were (4.77±0.33) h (CYX), (5.77±0.56) h (BDCYX), (4.12±0.28) h (CYX-1-O), and (8.51±0.39) h (QCA), respectively. After p.o. administration, C max s of (0.033±0.002) μg mL-1 (CYX), (0.22±0.03) μg mL-1 (BDCYX), (0.089±0.005) μg mL-1 (CYX-1-O), and (0.17±0.01) μg mL-1 (QCA) were observed at T max of (7.38±0.33) h (CYX), (7.25±0.31) h (BDCYX), (7.38±0.33) h (CYX-1-O), and (7.25±0.31) h (QCA), respectively. The results showed that CYX was slowly absorbed after oral administration and most of CYX was transformed to its metabolites in swine. The area under plasma concentration-time curve (AUC 0-∞ )of metabolites were higher than that of CYX after p.o. administration, and the elimination half-lives (t 1/2λz ) of QCA were longer than those of CYX, CYX-1-O, and BDCYX after oral administration.     

Study on Pharmacokinetics of Eprinomectin in Sheep Following Intravenous and Subcutaneous Administration

A RP-HPLC method was used for the determination of eprinomectin concentration in sheepplasma following i.v. and s.c. administration at a single dose of 0. 2 mg kg-1. Eprinomectin in plasma within2.5 - 200 ng mi-1 ranges had a good linear relationship(R=0. 9968). The average recovery of the method was99.65±3.84%. The RSD% of within-day and between-day assays were less than 10 and 12%, respectively.The extract of plasma samples were loaded onto a C18 catridge. After solvent exchange, the methanol eluatewas derivatized via the addition of 1-methylimidazole and trifluoroacetic anhydride in acetonitrile. The fluo-rescent derivative was analyzed. The main pharmacokinetic parameters were as follows, for i.v. administra-tion: T1/2β =12. 66± 2. 05 h, AUC0-t = 1.02 ± 0.3 mg h L-1 , fc =0. 13+0.05; for s.c. administration:T1/2sa = 4.42 ±l. 04 h, Cmax =0. 02±0.01 μg mi-1 , Tmax = 15.36 ± 2.91 h, t1/2K=26. 22±9.04 h, AUC0-t= 1.19±0.37 mg h L-1. The results showed that eprinomectin was distributed widely and taken long time toeliminate in sheep after i. v. adminstration. When given subcutaneously, eprinomectin had better absorptionand longer residue time in sheep. Eprinomectin was eliminated much slowly after s. c. adminstration comparedwith i.v. administration.     

Pharmacokinetics of Milbemycin Oxime in Dogs Following Its Intravenous and Oral Administration

The pharmacokinetics of milbemycin oxime was investigated in dogs following oral(per os, PO) and intravenous(IV) administration. Three groups of dogs received milbemycin oxime tablets as a single PO dose equal to 0.25, 0.5 and 1.0 mg · kg-1 of milbemycin oxime, respectively, another group received a single IV dose of 0.5 mg · kg-1. Blood samples were collected at predetermined times after drug administration and the milbemycin oxime concentrations in plasma were determined by LC-MS/MS. The drug protein binding in dog plasma in vitro was determined by equilibrium dialysis at concentrations spanning the range of values observed in vivo in dog plasma. After PO administration at doses of 0.25, 0.5 and 1.0 mg · kg-1, milbemycin oxime was slowly absorbed and eliminated, the time to reach the maximum plasma concentration(Tmax) was 4.14±0.20, 4.27±0.14 and 4.06±0.13 h, the mean absorption time(MAT) was 19.06, 13.67 and 11.77 h, the terminal rate half-life(t1/2λz) was 15.06±0.37, 11.09±0.54 and 9.76±0.89 h and the total body clearance(Cl) was 1.15±0.05, 1.18±0.03 and 1.17±0.07 m L · min-1 · kg-1, respectively. The maximum plasma concentration(Cmax, 36.50±1.40, 76.11±2.77 and 182.05±7.20 ng · m L-1, respectively) and the area under the first-moment curve(AUC-10→∞, 985.83±49.46, 1 663.12±51.42 and 3 558.04±197.88 mg · h · L, respectively) increased accordingly to the administered dose rates; the oral bioavailabilities were estimated to be 88.61%, 74.75% and 79.96%, respectively. The values of fu were 0.12%, 0.14% and 0.13% in dog plasma, respectively. In conclusion, the pharmacokinetics of milbemycin oxime in dogs following oral administration revealed its higher oral bioavailability and advantageous pharmacokinetic properties, such as its lower total body clearance and longer elimination half-life, and indicated that the single oral dose of 0.50 mg · kg-1 of milbemycin oxime which was recommended in all the parasitological efficacy studies allowed an adequate concentration of the drug.     

Pharmacokinetics and Residues of Cefquinome in Milk of Lactating Chinese Dairy Cows After Intramammary Administration

The purpose of the study was to investigate the pharmacokinetics of cefquinome in plasma and milk samples of lactating Chinese Holstein following a single intramammary administration into one quarter at the dose of 75 mg. Residue depletion of cefquinome in milk administrated at one quarter following three consecutive infusions at the same dose were also carried out. Cefquinome concentrations in plasma and milk were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） method. A non-compartmental analysis was used to obtain the pharmacokinetic parameters of cefquinome. Following the single treatment, cefquinome wasn’t detected in any of the plasma samples. The concentration of cefquinome in milk reached peaked values （Cmax） of （599.00±322.00） μg mL-1 at 2 h after administration （Tmax）, elimination half-life （t1/2λz） was （4.63±0.26） h, area under the concentration-time curve （AUC0-∞） was （4 890.19±1 906.98） μg mL-1 h, and mean residence time （MRT） was （6.03±2.27） h. In residue depletion study, cefquinome concentrations in 5 out of 6 milk samples at 72 h were lower than the maximum residue limit ifxed by the European regulatory agency （20μg kg-1 for cefquinome） and cefquinome still could be detected in milk of treated quarters at 120 h post-treatment. The maximum concentration （Cmax） of cefquinome in milk from treated quarters was （486.50±262.92） μg mL-1 and arrived at 6 h after administration （Tmax）, elimination half-life （t1/2λz） was （6.30±0.76） h, area under the concentration-time curve （AUC0-∞） was （44 747.79±11 434.43） μg mL-1 h, and mean residence time （MRT） was （10.09±1.40） h. This study showed that cefquinome has the feature of poor penetration into blood and was eliminated quickly from milk in lactating cows after intramammary administration.     

Determination of Forchlorfenuron Dissipation and Residue in Cucumbers and Red Soil

To assess the risks of forchlorfenuron after application, a residue analysis method for ferchlorfenuron in cucumbers and the red soil of Southern China was established, and the dissipation behavior and residue characteristics of forchlorfenuron were studied under field conditions. The field trials, including dissipation and residue experiments, were conducted in Hunan, Yunnan and Hainan Provinces. Forchlorfenuron was applied at 32 a.i.g ha-1 rate for the dissipation study and both 21 and 32 a.i.g ha-1 for the residue study. Representative cucumbers and soil samples were collected at predetermined intervals for HPLC for UV-detector analysis. The average recoveries of the method were 80.8%-92.0% with coefficients variation (CV) between 0.4% and 11.8%. The detection limit of forchlorfenuron in cucumbers and soil samples was 0.003 mg · kg-1 and the minimum detectable amount was 3.0×10-10 g. The half life of forchlorfenuron in cucumbers in the three provinces changed as: Yunnan (5.50 days), Hunan (5.88 days), and Hainan (6.53 days) and in the soil was observed: Hainan (6.54 days), Hunan (7.64 days), and Yunnan (8.39 days). The maximum terminal residue in cucumbers at 32 a.i.g ha-1 rate after 5 days was 0.009 mg · kg-1 (Yunnan) followed by 0.0085 mg · kg-1 (Hainan) and 0.0082 mg · kg-1 (Hunan) which was below MRL value of 0.01 mg · kg-1 established by the USA, EPA. So a waiting period of 5 days should be established after spaying on cucumbers to avoid hazard to human beings.     

Evaluation of Post-operative Anti-stress Response of Dexmedetomidine in Dogs

The stress response, caused by postoperative pain, may have adverse effects on physiological functions of bodies. And, it has been a research priority in veterinary anesthesia that is a method of minimizing the postoperative stress response. The paper aimed to explore the protective effect of dexmedetomidine on stress induced by surgical trauma by studying the effect of dexmedetomidine on the blood glucose, serum cortisol(Cor) and adrenocorticotropic hormone(ACTH) levels in the model of canine stress induced by surgical trauma. Therefore, 32 local healthy female dogs with similar physical conditions, aged from 11.3±2.4 months and mean body mass(±SD)(7.7±2.2) kg, were randomly divided into four groups: control group DZ(10 min after administration of intramuscular injection of 2 m L normal saline), group SQY(10 min before administration of intramuscular injection of 20 μg· kg~(-1) dexmedetomidine), group SHY(10 min after administration of intramuscular injection of 20 μg· kg~(-1) dexmedetomidine) and group DLD(10 min after administration of intramuscular injection of 0.1 m L · kg~(-1) tilidine). The corresponding drug was sucked out and diluted to 2 m L by saline. The four groups were all excised the uterus and ovaries and established surgical trauma stress model, then given the prescribed dose of the drug on the day of operation, the next day and the 3 rd day. Besides, the dogs should be fasted during the days of drug administration. Blood samples were separated and taken to measure, blood glucose, serum Cor and ACTH concentration. The concentration of blood glucose was significantly lower in group SHY than that in group DZ on the day of surgery and the day after surgery(p0.05), besides, it was not obviously different from other two groups. While, the concentration of Cor in group SHY had no significant differences from other three groups(p0.05) and was closer to the preoperative values; ACTH concentration in group SHY was significantly different from other three groups on the day of operation(p0.05), and there existed significant difference(p0.05) with group DZ on the 2 nd day after the operation. The results of analyses showed that 20 μg· kg~(-1) dexmedetomidine could decrease the levels of Cor and ACTH in dog serum after operation, which played the role of anti-stress response stimulated by operations.     

Effects of Probiotics on Growth,Pork Quality and Serum Metabolites in Growing-finishing Pigs

A total of 72 growing-finishing pigs（56 days old） were used to investigate the effects of dietary probiotics on growing performance, pork quality and serum metabolites. Using single factorial experiment design, pigs were allotted to three groups（four pens/group and six pigs/pen）. Diet treatments were a corn-soybean meal（control group） and a corn-soybean meal with 1% probiotics（probiotics group） or 80 mg kg-1colistin sulfate（antibiotics group）. Pigs were slaughtered when pigs of the lightest averaged 90 kg（157 days of age）. There was no difference（p＆gt;0.05） in average daily gain or feed/gain, and the average daily feed intake of the antibiotics group was higher than that of the probiotics and the control groups（p＆lt;0.05）. Diet supplemented with probiotics reduced the drip loss and cooking loss of pork（p＆lt;0.05）. Dietary supplementation with probiotics significantly decreased the content of triglycerides, lowdensity lipoprotein and urea nitrogen in serum（p＆lt;0.05）, and increased the content of high-density lipoprotein in serum（p＆lt;0.05）. These results suggested improving effects of dietary probiotics on pork quality and serum metabolism in growing-finishing pigs.     

Effect of Eliminated the Breeding Pigs with Unqualified CSFV Antibody on Sows＇ Reproductive Performance and Pigs＇ Growth Performance

[Objective] The aim was to explore the effect of eliminated the breeding pigs with unqualified CSFV antibody on sow’s reproductive performance and pig’s growth performance so as to provide a scientific basis for the eliminating of the breeding pigs with unqualified CSFV antibody in large-scale pig farms.[Method] Serum samples from three scale pig farms were collected and tested with HerdChek CSFV-ELISA kit,then provided a certain scientific basis for scale pig farm to eliminate the unqualified(antibody blocking rate<50%)breeders after booster immunization.[Result ] After eliminating the breeding pigs with unqualified CSFV antibody,the average litter number of piglet in three pig farms(A,B,C)were increased by 0.29(P<0.05),0.40(P<0.01),0.39(P<0.01)respectively;the average number of survival piglets were increased by 0.54(P<0.01),0.35(P<0.01),0.62(P<0.01)respectively;the average litter number of weaned piglets were increased by 0.65(P<0.01),0.71(P<0.01),0.81(P<0.01)respectively.The difference in weight gain of piglet at 30-60 d of age was extremely significant(P<0.01),but inconspicuousness for the swine pregnancy rate,the survival rate of weaned piglet and piglet at 30-60 d of age.[Conclusion] The eliminating the breeding pigs with unqualified CSFV antibody can significantly improve the performance of breeder and piglets.     

Immunotoxicity assessment of cadinene sesquiterpenes from Eupatorium adenophorum in mice

Sesquiterpenes in Eupatorium adenophorum are abundant in leaves and have great development potential as biopesticides. The toxicity of sesquiterpenes in immune cells and their corresponding immune functions are not fully understood. We evaluated the immunotoxicity of two cadinene sesquiterpenes 2-deoxo-2-(acetyloxy)-9-oxoageraphorone(DAOA) and 9-oxo-10,11-dehydro-agerophorone(ODA) by using histopathology and toxicology methods in vitro and in vivo in lymphocytes and natural killer cells in Kunming mice. The mice were given single doses of 75, 150 and 300 mg kg-1 body weight(BW) of DAOA/ODA every day for a week. S erious damage to the thymus and spleen was found in tissue images with clear lysis reduction numbers and a loosened arrangement of splenocytes and thymocytes to the mice treated with 150–300 mg kg-1DAOA/ODA. Mice cytology was also affected with significant cellular alterations, increased splenocytes apoptosis rates(P0.01), proliferation reduction(P0.05) and natural killer cells activities reduction(P0.05) when given 150–300 mg kg-1DAOA/ODA, the severities of which were dose-dependent. Howev er, a 75 mg kg-1 dose of DAOA/ODA showed no change in tissue or cytology after the 7 day treatment, and therefore was considered to be within acceptable safety parameters. Taken together, cadinene sesquiterpenes, as a type of toxic botanical component, have low environmental risks in small doses and should be further studied for their use as biopesticides.     

Studies on the Injectable Solution of Colistin Sulfate and Its Pharmacokinetics

The present studies were conducted to compose an injectable solution of colistin sulfate containing local anaesthesia, antioxidant and other additions. Results showed that the novel preparation was stable either to heat or to light. The term of validity of the preparation was 2 years at room temperature.The preparation containing 25.0 mg ml-1 colistin sulfate showed no local tissue irritation, but the concentration of 50. 0 mg ml-1 colistin sulfate showed obvious local tissue irritation. Result of acute toxicity test showed that the LD50 of intramuscular injection in mice was 38. 72 mg kg-1 , and oral LD50 was 431.39 mg kg-1. The evidence of neurotoxicity was observed in mice in the acute toxicity test. A dose of 10.0 mg kg-1 b.w. or 15:0 mg kg-1 b.w. was administered intramuscularly to piglet once daily for 5 days. No changes were detected in the piglet body except for the slight epithelial tissue's granular degenerations in the kidney and liver at the dose of the 10. 0 mg kg-1. While at the dose of 15.0 mg kg-1 , the obvious neurotoxicity was observed at 4 - 5 days. The epithelial tissues in the kidney and liver showed moderate granular degenerations, especially in the tubuli renales cells. Blood cell's morphosis indexes were normal. With relation to liver's function, the indexes went beyond the normal scope. But with relation to kidney's function, the indexes showed mostly normal.When the preparation was separately administered into muscle(i. m. ) in piglets with the dose of 2.5 and 5.0 mg kg-1 b. w, whose Cmax were 3.73±0. 28 and 6. 40±0. 18 μg ml-1; Tmax were 32±1.5 and 34±1.8min;t1/2β were 256±14 min and 264±29 min, respectively. t1/2β was 251±13 min for the injection given into aural vein(i. v. ) with the dose of 2.5 mg kg-1 b.w.. Samples of the experimentally determined plasma concentration of colistin sulfate generated two-exponential model with first-order absorption. The mean absolute bioavailability coefficient of 2.5 and 5.0 mg kg-1 b. w. (i. m. ) were 98. 30 and 88.54%, respectively. The high bioavailability and the long maintaining time of the valid blood-drug concentration showed that the injectable solution was suitable for i.m. in pigs, whose recommended dose was 2.5 mg kg-1 b. w., twice daily.     

泰妙菌素混悬注射液在猪体内的药物动力学及生物利用度研究

 【目的】 研究并比较泰妙菌素混悬注射液和泰妙菌素注射液在猪体内的药物代谢动力学特征及生物利用度。【方法】 7头健康猪,按随机拉丁方设计,进行单次给药剂量(10 mg&#8226;kg-1 b.w)静注、肌注泰妙菌素注射液和肌注泰妙菌素注射混悬液,高效液相色谱串联质谱法测定猪血浆中泰妙菌素的浓度,罗红霉素作为内标,3P97药动学计算软件处理血浆药物浓度－时间数据。【结果】 猪静注给药的药时数据符合无吸收三室开放模型,主要药动学参数为：t1/2β为2.04±0.23 h,t1/2α为0.39±0.06 h,t1/2π为0.12±0.04 h,Vd 为8.73±1.83 L&#8226;kg-1,AUC为3.78±0.52μg&#8226;mL-1&#8226;h-1,ClB为2.99±0.43 L&#8226;kg-1&#8226;h-1)。猪肌注泰妙菌素注射液的药时数据符合一级吸收二室开放模型,主要的药物动力学参数分别为：t1/2Ka(0.06±0.01)h,t1/2β(3.67±0.41)h,Tmax(0.18±0.03)h,Cmax(1.32±0.25)μg&#8226;mL-1,AUC(2.62±0.21)μg&#8226;mL-1&#8226;h-1,生物利用度为73.51%。猪肌注泰妙菌素混悬液的药时数据则符合一级吸收一室开放模型,主要的药物动力学参数为：t1/2Ka(0.04±0.01)h,t1/2Ke(2.90±0.43)h,Tmax(0.27±0.03)h,Cmax(0.7±0.11)μg&#8226;mL-1,AUC(2.80±0.35)μg&#8226;mL-1&#8226;h-1,生物利用度为75.73%。t检验比较肌注泰妙菌素注射液和泰妙菌素注射混悬液的主要药动学参数,结果表明,两者除达峰浓度Cmax有显著差异外,AUC、t1/2Ka、Tmax、t1/2Ke和生物利用度均无显著性差异。【结论】泰妙菌素注射混悬液肌注后在猪体内具有吸收迅速,体内分布广,达峰迅速,消除较快的药动学特征。     

盐酸林可霉素-硫酸大观霉素混悬注射液在猪体内的药动学研究

8头健康猪按体质量单次深部肌内注射盐酸林可霉素-硫酸大观霉素(5 mg.kg-1林可霉素,10 mg·kg-1大观霉素)混悬注射液后,用高效液相色谱法分别测定林可霉素和大观霉素的血药浓度,使用非房室统计矩分析方法处理得到血药浓度-时间数据.林可霉素主要药动学参数分别为:ke=(0.21±0.01)h-1;t1/2β=(3.38±0.09)h;tmax=(0.29±0.02)h;Cmax=(5.15±0.18)μg·mL-1;AUC0～LOQ=(10.27±0.38)μg·mL-1.h;MRT=(3.52±0.11)h;ClB/F=(0.46±0.01)L·h-1·kg-1;VZ/F=(2.26±0.12)L·kg-1.大观霉素主要药动学参数分别为:ke=(0.43±0.01)h-1;t1/2β=(1.64±0.06)h;tmax=(0.44±0.03)h;Cmax=(20.05±0.70)μg·mL-1;AUC0～LOQ=(51.82±0.98)μg·mL-1·h;MRT=(2.39±0.04)h;ClB/F=(0.19±0.01)L·h-1·kg-1;VZ/F=(0.46±0.02)L·kg-1.结果表明,肌内注射盐酸林可霉素-硫酸大观霉素混悬注射液后,两药均迅速吸收并快速消除,但后者吸收稍慢,消除较快.     

氟苯尼考颗粒与氟苯尼考粉在猪体内的药物动力学比较

健康猪14头随机分为A、B2组,分别单剂量胃管灌服氟苯尼考粉和颗粒,按体质量给药剂量均为30 mg/kg,进行比较药动学研究.高效液相色谱法(HPLC)测定其血药浓度.采用药动学分析软件WinNonlin 5.2.1的非房室模型处理血药浓度-时间数据.氟苯尼考粉灌胃给药的主要药物动力学参数为:t1/2β=(10.22±0.18)h,ke=(0.07±0.01)h-1,tmax=(1.67±0.48)h,Cmax=(24.68±1.13)μg·mL-1,AUC=(190.97±16.60)μg·mL-1·h,MRT=(8.33±0.42)h,tcp=(17.66±1.52)h.氟苯尼考颗粒灌胃给药的主要药物动力学参数为:t1/2β=(16.36±4.14)h,ke=(0.05±0.01)h-1,tmax=(5.71±0.47)h,Cmax=(12.23±0.78)μg·mL-1,AUC=(155.44±6.59)μg·mL-1·h,MRT=(14.96±0.35)h,tcp=(23.03±0.49)h.试验结果表明,与氟苯尼考粉相比,氟苯尼考颗粒的消除半衰期更长,有效血药浓度维持时间也较长.     

马波沙星在罗非鱼体内的药物代谢动力学研究

【目的】研究马波沙星在罗非鱼Oreochromis niloticus体内的药物代谢动力学(简称药动学)特征,为临床合理用药提供参考。【方法】将罗非鱼随机分成2组,水温维持在30℃,以10 mg·kg-1分别单剂量肌内注射和口服给药,高效液相色谱(HPLC)-荧光检测法测定血浆中马波沙星的质量浓度,用Win Nonlin 6.1药动学软件的"非房室模型"分析药动学参数。【结果】肌内注射马波沙星后,药物吸收和消除均较口服快,体内分布广泛。达峰时间(tmax)为0.25 h,峰质量浓度(ρmax)为4.31μg·mL~(-1),消除半衰期(t1/2λz)为19.21 h,表观分布容积为3.94L·kg-1,药-时曲线下面积(AUC)为70.36μg·mL~(-1)·h-1。口服马波沙星后,药物吸收和消除均较慢,体内分布广泛。tmax为4.00 h,ρmax为2.45μg·mL~(-1),t1/2λz为22.67 h,表观分布容积为4.27 L·kg-1,AUC为76.66μg·mL~(-1)·h-1。【结论】10 mg·kg-1马波沙星能够有效治疗大多数敏感菌引起的罗非鱼感染。     

司帕沙星在实验性感染大肠杆菌-败血霉形体病鸡体内的组织动力学及残留研究

实验性感染大肠杆菌—败血霉形体病鸡,单剂量(5 mg.kg-1)内服司帕沙星,研究其组织动力学和残留情况。采用HPLC面积-内标法测定各组织中司帕沙星浓度,利用药动学分析软件MCPKP分析药-时数据。疾病模型鸡肝脏、肺脏和心脏中的药—时数据符合一级吸收三项指数方程,主要动力学参数为:t1/2α0.3505,0.8381,0.6005 h;t1/2β11.7802,13.8479,2.4578 h;tmax 1.0653,1.1397,0.7546 h;Cmax 3.3591,2.2951,1.7226μg.mL-1;AUC24.4230,30.663,5.3780 mg.L-1.h-1,Tcp(ther)81.0240,108.52,18.410 h。肾脏和肌肉组织中药-时数据符合一级吸收二项指数方程,主要动力学参数为:t1/2K 2.2287,7.5072 h;tmax1.4655,1.8644 h;Cmax1.9926,1.1317μg.mL-1;AUC9.8536,14.5240 mg.L-1.h-1;Tcp(ther)19.923,58.156 h。各组织中药物浓度降至0.001 mg.kg-1时需休药7 d。     

恩诺沙星在异育银鲫体内的组织分布及消除规律

在24～26℃水温条件下,以10 mg.kg-1剂量,用高效液相色谱法检测组织中药物浓度,研究静脉注射和口服给药后恩诺沙星在健康异育银鲫组织内的代谢分布规律。结果表明:静脉注射后,药物在组织中代谢动力学特征符合二室模型;口服给药后,药物吸收良好,生物利用度(F)为86%,组织药物浓度-时间曲线呈现双峰,推测是由于药物在异育银鲫体内的肠肝循环作用所致。静脉注射和口服两种给药方式下,恩诺沙星在异育银鲫体内均具有良好的组织分布,肾脏、肌肉、肝胰脏、鳃和血液5种组织中的药物浓度时间曲线下总面积(AUC)分别为624.2、965.9、721.8、298.0、239.6μg·h·mL-1和465.3、343.1、542.9、411.4、205.9μg·h·mL-1,最大药物浓度(Cmax)分别为33.48、16.91、26.44、18.71μg.g-1和15.30μg·mL-1,9.20、5.39、7.78、6.88μg.g-1和4.50μg·mL-1;药物在各组织中消除时间较长,消除半衰期(T1/2β)分别为169.0、141.4、113.4、36.7、63.5 h和27.3、49.2、77.0、38.5、62.7 h。结论:恩诺沙星以10 mg.kg-1剂量单次口服给药,对细菌引起的异育银鲫病可以起到较好的治疗作用,但需注意药物残留问题。     

洛克沙胂在鸡体内的药物动力学和生物利用度研究

50日龄健康岭南三黄肉鸡24只随机分为2组,雌雄各半.分别进行单剂量(10 mg.kg-1)静注和内服洛克沙胂的药物动力学(简称药动学)研究.以反相高效液相色谱法测定血浆中洛克沙胂质量浓度,采用WinNonlin 5.2药动学软件的非房室模型统计矩原理分析药物质量浓度-时间数据.鸡静注给药后主要药动学参数为:t1/2β=(2.37±0.11)h,Vz=(5.29±0.37)L.kg-1,AUC0-∞=(6.55±0.28)mg.L-1.h,CL=(1.56±0.07)L.h-1.kg-1.内服给药的主要药动学参数为:t1/2β=(3.02±0.08)h,tmax=(1.00±0.07)h,Cmax=(1.09±0.08)mg.L-1,AUC0-∞=(2.30±0.10)mg.L-1.h,MRT=(2.44±0.13)h,F=(35.28±1.0)%.洛克沙胂在鸡体内的药动学特征表现:静注分布较为广泛,消除迅速;内服给药后,吸收较快但不完全,生物利用度较低.     

Pharmacokinetics of Quinocetone and Its Major Metabolites in Swine After Intravenous and Oral Administration

The pharmacokinetics of quinocetone and its major metabolites in healthy swine was investigated in this paper.Quinocetone was administered to 8 healthy cross-bread swine intravenously and orally at a dosage of 4 and 40 mg kg-1 body weight respectively in a randomized crossover design test with two-week washout period.A sensitive highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed for the determination of quinocetone and its metabolite 1-desoxyquinocetone in plasma.Plasma concentration versus time profiles of quinocetone and its metabolite l-desoxyquinocetone were analyzed by non-compartmental analysis using Winnonlin 5.2 software.Mean maximum concentrations (Cmax) for quinocetone was found to be (0.56±0.13) μg mL-1 at 2.92 h,after oral administration of quinocetone.Mean maximum concentrations (Cmax) for l-desoxyquinocetone after intravenous or oral administration of quinocetone were (0.0095±0.0012) μg mL-1 at 0.083 h and (0.0067±0.0053) μg mL-1 at 3.08 h.The apparent elimination half-lives (T1/2) for quinocetone and its metabolite 1-desoxyquinocetone were (2.24±0.24) and (5.23±0.56) h after intravenous administration of quinocetone and (2.91±0.29) and (11.85±2.89) h after oral administration of quinocetone,respectively.Mean areas under the plasma concentration-time curve (AUC0-∞) for quinocetone and 1-desoxyquinocetone were (2.02±0.15) and (0.2±0.002) μg h mL-1 respectively after intravenous administration of quinocetone,and (3.5±0.79) and (0.053±0.03) μg h mL-1 after oral administration of quinocetone,respectively.Quinocetone was rapidly absorbed and metabolized in swine after oral and intravenous administration.The plasma concentration-time curve (AUC0-∞) of 1-desoxyquinocetone were much smaller than those of quinocetone,while the elimination half-lives (T1/2) were much longer than those of quinocetone after intravenously (i.v.) or oral administration.     

复方茵芩制剂中黄芩苷的药代动力学研究

探讨复方茵芩制剂有效成分黄芩苷在小鼠体内的药物代谢动力学特征,按16.5 g.kg-1(相当于黄芩苷239.5 mg.kg-1)的剂量给小鼠口服复方茵芩制剂,用高效液相色谱法(HPLC)检测用药后0.25、0.5、1.0、2.0、3.0、4.0、5.0、6.0、8.0、12.0、14.0、16.0、20.0、24.0、36.0、48.0、72.0 h血浆中药物黄芩苷的质量浓度,研究在小鼠体内的药物代谢动力学.结果表明,复方茵芩制剂中黄芩苷在小鼠体内的药时数据符合开放性二室模型,动力学方程为:C=16.76 e-0.45t+3.10 e-0.03t-20.99 e-2.13t;主要药代动力学参数:T1/2α1.54 h,T1/2β5.25±2.96 h,T1/2 Ka0.34 h,AUC0→∞128.99 mg.L-1.h-1,CL/F0.19 L.h-1,Vd/F6.363 L.kg-1,Tpeak1.05 h,Cmax11.19μg.mL-1.     

双氢杨梅素在家兔体内的药动学研究

[目的]研究双氢杨梅素在家兔体内的药动学特征。[方法]经单剂口服给药后,收集家兔血样,经离心后,采用紫外分光光度法于280 nm波长处进行血药浓度测定。[结果]双氢杨梅素的血药浓度—时间曲线符合一级消除的单室模型,Ke为(0.76±0.13)h-1,Ka为(0.85±0.24)h-1,t1/2(Ka)为(0.82±0.31)h,t 1/2(Ke)为(0.91±0.44)h,Tmax为(1.5±0.46)h,Cmax为(12.36±2.7)mg/L,AUC0→∞为(45.45±22.3)mg.h/L,CL/F为(4.71±1.21)L/(h.kg),V/F为(6.17±3.12)L/kg。[结论]该方法简便、可靠、灵敏,适用于双氢杨梅素的药动学研究。