不同剂量阿普唑仑在大鼠体内的药动学研究

3组大鼠分别按50、20和2 mg·kg~(-1)阿普唑仑悬液,ig,体内动力学特征均符合一室开放模型.各组的吸收和消除参数无明显差异,平均值(n=18)K_a=3.3454 h~(-1).K.=0.3873 h~(-1),T_((1/2)k_(?))=0.29 h,T((1/2)K_(?))=2.61h,T_(max)=1.04 h。血药浓度与给药剂量呈正相关,3组的C_(max)(n=6)分别为4.5764、2.1793和0.2256μmol·L~(-1),r=0.6096(P<0.005);AUC分别为28.31、8.42和2.13 h·μmol·L~(-1),r=0.6854(p<0.001)、各剂量组的血药浓度和药动学参数均存在较大个体差异。     

阿洛西林在狗的药物动力学参数的反相高效液相色谱法测定

本文用反相高效液相法测定犬静注和肌注阿洛西林20mg/kg后的血中药物浓度,并据此计算有关药物动力学参数。ODS-C_(18)为固定相,甲醇/67mmol/L磷酸缓冲液(1:1,vol/vo1)为流动相,紫外(uv)检测。以对硝基丙酰苯胺为内标物对血清中阿洛西林进行定量测定。根据F值,r 2/1值和AIC(Akaike's Information Criterion)值判断静注和肌注药物后在体内的转运过程分别符合开放型二室和一室模型。静注后即刻血药浓度为218±13μg/mL,T_(1/2α)为0.13h。肌注后T_(max)和T_(1/2ka)分别为0.75和0.24h,C_(max)为16±6μg/mL,但im后AUC仅为iv相同剂量后的38％。该药iv和im后的T_(1/2)分别为1.5和1.7h,V_d分别为0.35和0.43L/kg。本实验结果与微生物法测定结果间无显著差异。     

稳定同位素结合GC-MS法测定大鼠体内川芎哚的药物动力学参数(英文)

目的:测定川芎哚(川芎Ⅲ号碱,perlolyrine)的药动学参数。方法:以[2-~(15)N]川芎哚为内标准及GC-MS的SIM(选择性离子监测)为检测手段,定量测定大鼠体内川芎哚的含量及其药代动力学参数。结果:大鼠灌胃给予川芎哚2mg·kg~(-1)后,川芎哚在大鼠体内呈二室模型分布,其药代动力学参数为:T_((1/2)α)=0.33h,T_((1/2)β)=4.52h,T_(1/2)(ka)=0.14h,T_(max)=0.35h,C_(max)=18.84μg/L,K_(12)=0.88h~(-1),K_(21)=0.42h~(-1),K_(10)=0.32h~(-1),V/F=109.22 L·kg~(-1),AUC=112.68μg·h·L~(-1)。结论:本法灵敏度高、特异性强且准确性好,为测定川草哚药代动力学参数提供了实用的分析方法。本研究为川芎哚临床应用提供了重要的参考资料。     

葡萄糖酸钙片的人体药物动力学研究

用原子吸收分光光度法测定人体口服葡萄糖酸钙片后的血钙浓度,其体内过程符合一室模型。主要动力学参数为:k_a=2.874 h~(-1);k_e=2.396 h~(-1);T_(2ke)~1=0.291 h;T_(max)=1.175 h;C_(max)=8.995μg/ml;AUC=9.638mg/(L·h);V=0.135 L;CL=0.333 Lh~(-1);T_(lag)=0.768 h;初步认为缺钙患者的临床给药方案应为每次 Ca~(2 )3 mg/kg,每1.5 h一次。     

国产氧氟沙星在健康成人中的药物动力学和生物利用度研究

本文采用专一性强、灵敏度高的HPLC 荧光检测法,测定氧氟沙星血、尿浓度。对国产氧氟沙星片在12例健康受试者中进行药物动力学和生物利用度研究。氧氟沙星片口服给药多数人为一房室模型,其主要药动学参数,国产片和进口片分别为:T_(1/2)6.2±1.3和6.1±1.5h;Vd 1.5±0.4和1.6±0.5l/kg;C_(max)8.6±2.5umol/L 和7.9±1.4μmol/L;T_(max)0.6±0.5和0.6±1.0h;Cl_T13±4和12±4 l/min;AUC_(o-∞)76±23和73±21μmol/L·h。其相对生物利用度为104.9±9.9%。     

苯妥英钠与卡马西平在健康志愿者体内药物动力学相互作用

应用高效液相色谱法测定16名健康志愿者单用和联用苯妥英钠和卡马西平的血浓度。动力学过程用一房室模型一级动力学拟合。首次报道中国人体内苯妥英钠和卡马西平相互作用引起的2药最大稳态浓度C_((ss)max),最小稳态浓度C_((ss)min),达峰时间T_(max),消除半衰期T_(1/2),药时曲线下面积AUC等动力学参数变化的资料。结果表明苯妥英钠使卡马西平的T_(1/2)明显缩短,而卡马西平则延长苯妥英钠的T_(1/2)。     

对乙酰氨基酚咀嚼片相对生物利用度测定

2名健康受试者一次po两种对乙酰氨基酚咀嚼片后,用高效液相法测定ab的血药浓度。其血药农度和过程符合一室模型。国产对乙酰氨基酚咀嚼片A(tempra A)的药代动力学为:T1/2Ka=0.3806±0.2816h,T_(1/2)K_e=1.761±0.8930h,T_(max)=0.9023±0.4179h,C_(max)=7.0728±1.2264mg/L AUC=26.8579±10.7680μg·ml~(-1)·h~(-1)。tempra B的药代动力学为:T_(1╱2)Ka=0.2993±0.2584h,T_(1╱2)Ke=1.9720±0.470h,T_(max)=0.8322±0.5263h,C_(max)=6.7487±2.1925mg/L,AUC=25.0871±5.7059μg·m1~(-1)·h~(-1),国产对乙酰氨基酚痛咀嚼片与进口对乙酰氨基酚咀嚼片B(tempra B)的相对生物利用度为107.06％。提示两种对乙酰氨基酚咀嚼片的生物利用度相仿。     

丙戊酸钠缓释片在5例癫痫儿童的药物动力学

对5例接受丙戊酸钠缓释片(20～25mg·kg~(-1)·d~(-1),qn,po)治疗的初诊癫痫儿童(5～11a)进行药物动力学研究.结果:单剂量服药后,T_(max)=6.59±2.2h,C_(max)=67.43±8.32mg/L,C_(min)=30.91±7.39mg/L,T_(1/2(β))=13.29±4.19h,AUC=1771±380mg/(L·h),T_(lag)=2.14±1.42h.治疗d10,服药后12,24h,血VPA浓度各为113.10±8.56,68.36±9.62mg/L,均较第1次服药时高,P<0.001,可24h内维持血VPA浓度在较高有效治疗范围.     

口服洛美沙星的人体药物动力学

目的:研究健康志愿者单剂po国产洛美沙星400mg后的药物动力学特征.方法;采用HPCL法测定血清和尿中药物浓度.结果:该药在人体内的转运过程符合二室开放模型,C_(max)为 4.88 mg/L,T_(1/2β)为 7.19 h,Vd和AUC分别为 1.51L/kg和51.03(mg·h)/L,CL为 2.47 d/(min·kg),48h尿药排泄率为75.7%.洛美沙星的人血清蛋白结合率为16.3%.结论:洛美沙星400mg单剂po后血和尿中可迅速达到有效抗菌浓度且持续时间较长.     

用微生物法测定环丙沙星血药浓度及稳态药物动力学

建立了人血清中环丙沙星的微生物测定法,平均回收率为101.2%,日内误差CV为4. 5%,以该法对患者进行了环丙沙星的稳态药物动力学研究,体内过程符合一室模型.其主要药物动力学参数为 T_(max)=0.96±0.44h;(C_∞)_(max)=2.73±1.02μg/ml;T_(1/2)=5.14±1.13h;Vd/F=6.62±4.18L/kg;Cl/F=0.89±0.52L/(kg·h).     

口服双氢青蒿素在兔和狗体内的药代动力学研究

青蒿素是一带有双氧桥结构的倍半萜内酯类抗疟药,已获我国卫生部新药审批委员会批准正式生产,用于临床。青蒿素用硼氢化钠还原得双氢青蒿素,其抗疟作用为青蒿素的4～8倍。我们曾报告给狗po青蒿素50mg/kg后,用放射免疫法在血中未测到青蒿素。     

正常人口服磷酸川芎嗪的药代动力学研究

本文建立了用高效液相色谱法测定人体内川芎嗪血药浓度的方法,以C18化学键合硅胶(10μgm)为固定相,以甲醇—水(58:42)为流动相,280 nm俭测,安眠酮为内标,进行定量测定,得出俭测限为3.5 ng(S/N=4),最低检测血清浓度为17.4 ng/ml,川芎嗪血药浓度在0.029～5.82μg/ml范围内,线性关系良好,方法回收率为99.84%。方法重现性好,专一性强,内源性物质、代谢产物及同时服用的药物均不干扰。用本法测定了健康人口服川芎嗪的药代动力学参数。     

Pharmacokinetics and tissue distribution of iv injection of polyphase liposome—encapsulated cisplatin（KM—1） in rats

目的:评价多相脂质体顺铂(KM-1)在大鼠体内的药物动力学及组织分布,并与游离顺铂比较。方法:用电感耦合等离子光谱法(ICP-AES)测定给药后大鼠血清及组织中铂的含量。结果:大鼠尾静脉给予4.5mg/kg剂量的KM-1后,血清-时间曲线符合开放三室模型。主要药动参数为:V_c=0.10L/kg,T_(1/2π)=0.3h,T_(1/2α)=3.5h,T_(1/2β)=2.7h,AUC-265mg·h·L~(-1),CL(s)=0.02g·L~(-1)·h~(-1)。多相脂质体顺铂从血清中的消除速率小于游离顺铂。药物在组织中的分布以肝、脾器官中的含量最高。结论:该药物具有一般脂质体的基本特性,在血液循环中停留的时间比游离药物长,且易被网状内皮系统丰富的组织器官吸收。     

溴泰君(W198)在大鼠和比格狗体内的药代动力学

目的研究溴泰君(W198)在大鼠和比格狗的药代动力学。方法采用HPLC紫外检测方法测定大鼠及比格狗注射W198后血清药物浓度。结果大鼠iv W198 10,20和40 mg·kg^-1 3个剂量的T_1/2β分别为6.60,7.36和6.77 h,AUC_0-24h分别为3.797,7.371和15.192 mg·h·L^-1,V_d分别为7.14,4.33和4.13 L·kg^-1,CL分别为2.83,2.60和2.71 L·(kg·h)^-1。大鼠im W198 20 mg·kg^-1后T_1/2β为11.61 h,AUC_0-24h为4.191 mg·h·L^-1,im的生物利用度为56.9%。比格狗iv W198 5 mg·kg^-1,T_1/2β为11.72 h,AUC_0-24h为12.646 mg·h·L^-1,V_d为0.70 L·kg^-1,CL为0.46 L·(kg·h)^-1。W198与人血浆蛋白的结合率平均为78.0%。结论W198 im的T_1/2β比iv的略长,其生物利用度为56.9%。在10～40 mg·kg^-1剂量内的吸收呈现一级动力学特征。     

盐酸戊乙奎醚外消旋体及其四个光学异构体在小鼠体内的分布与药代动力学

目的　研究盐酸戊乙奎醚外消旋体及其 4个光学异构体在小鼠体内的分布与药代动力学。方法　应用GC MS/SIM定量方法测定了盐酸戊乙奎醚外消旋体及其 4个光学异构体在小鼠脑、颌下腺及血浆中的药物浓度。结果　盐酸戊乙奎醚外消旋体在小鼠体内的血药时程符合一级吸收二室模型。其主要药动学参数为 :T1/ 2α0 2 3h ,T1/ 2 β3 2 8h ,T1/ 2Ka0 0 13h ,Tmax0 0 6 7h ,Cmax 18 76 μg·L-1,AUC5 0 4 2 μg·h·L-1。给药 8h后 ,盐酸戊乙奎醚外消旋体及其4个光学异构体在小鼠体内血药浓度存在差异。异构体R 2保持了相对较高的血药浓度。盐酸戊乙奎醚异构体在脑中的分布特点是与M受体亲和力较大的R 2异构体在脑中具有较高的分布浓度。R型异构体在脑中消除慢 ,而S型异构体在脑中消除快。盐酸戊乙奎醚在颌下腺中的分布特点为异构体S 1的分布浓度高 ,消除慢。结论　R及S型异构体在小鼠脑与颌下腺中的分布与mAChR的亲和力存在相关性。     

高效液相色谱法测定人血清中二甲胺四环素的浓度及其药代动力学研究

建立了反相高效液相色谱法测定二甲胺四环素的血药浓度。柱C18；以己腈-0．lmol／L枸橼酸溶液（15：85）为流动相，在353nm处测定。以土霉素为内标，血样在pH6．5条件下用乙酸乙酯提取；用二甲胺四环素与内标的峰高比进行定量。线性范围0．5～7μg／ml（Y=0．9994），最低检测限50ng／ml；平均回收率92．84％；日间RSD＜5％。应用本法研究了8名健康志愿者单次口服200mg盐酸二甲胺四环素胶囊后的药代动力学，符合二室开放模型，于2．4h达血峰浓度3．42±0．63μg／ml；AUC为77．12±16．89mg．h／L；t1/2为20．61±3．22h。     

Multiple dose pharmacokinetics of risperidone and 9-hydroxyrisperidone in Chinese female patients with schizophrenia

AIM: To study the multiple dose clinical pharmacokinetics of risperidone and its main active metabolite, 9-hydroxyrisperidone, in Chinese female patients with schizophrenia. METHODS: The subjects were 23 Chinese female inpatients aged 18-65 years who met the CCMD-III (third revision of the Chinese Criteria of Mental Disorders) criteria for schizophrenia. Subjects were tested after 17 d of treatment with 2 mg risperidone twice daily. Plasma concentrations of risperidone and 9-hydroxy-risperidone were assayed by using validated high performance liquid chromatography-mass spectrometry (HPLC-MS) methods. RESULTS: Risperidone was rapidly absorbed (Tmax was 1.6 h) and its T1/2 in plasma was short (3.2 h). 9-hydroxy-risperidone was quickly metabolized from the parent drug with a mean Tmax of 2.5 h. It had a long half-life of 24.7 h. The C(ss)(av) of risperidone and 9-hydroxy-risperidone were 36.9+/-33.1 and 110.6+/-30.5 microg x h x L(-1), respectively, and the AUC(ss)0-12 were 443.2+/- 397.4 and 1327.2+/- 402.3 microg x h x L(-1), respectively. CL/F and V/F of risperidone were 8.7+/- 6.2 L/h and 34.1+/- 24.3 L, respectively. Interindividual variations for pharmacokinetic parameters were quite large for risperidone. All 23 subjects experienced high prolactin levels when treated with risperidone. However there was no correlation between prolactin level and the concentration of risperidone, 9-hydroxy-risperidone, or the active moiety. CONCLUSION: Risperidone showed large interindividual variations in pharmacokinetics. Administration of risperidone resulted in high serum prolactin levels. The results indicate that systemic exposure to risperidone and 9-hydroxy-risperidone in female Chinese schizophrenic patients is higher relative to published data for white Caucasian patients. Larger studies regarding the PK/PD relationship may be required to develop a reasonable clinical dosage regimen for Chinese female patients.     

Laboratory and clinical studies on ceftizoxime in the field of pediatrics (author's transl)

Ceftizoxime, a new cephalosporin preparation, was evaluated for its antibacterial activity, absorption, excretion and clinical effectiveness, and the following results were obtained. The minimum inhibitory concentrations (MICs) of ceftizoxime against 211 clinical isolates were determined in comparison with those of cefazolin, cefmetazole, cefotiam and 6059 S. Against S. pyogenes (50 strains), ceftizoxime was 1 tube inferior to cefazolin inoculum size of 10(8) cells/ml, but was 2--3 tubes superior to cefmetazole and 6059-S. Against E. coli (50 strains), ceftizoxime and 6059-S were significantly more active than the other drugs. The susceptibility pattern of Klebsiella sp. (50 strains) to ceftizoxime was similar to that to cefotiam and 6059-S. Against Proteus sp. (50 strains), cefotiam and 6059-S were more active than the other drugs. Ceftizoxime was intermediate in activity, and cefazolin was the least active. Against H. influenzae (11 strains), ceftizoxime was the most active, with concentrations of 0.1 mcg/ml required to inhibit 100% of strains with an inoculum size of 10(8) cells/ml and 10(6) cells/ml. A dose of ceftizoxime 10 mg/kg or 20 mg/kg was administered to 15 patients aged from 5 years to 12 years, and serum levels and urinary excretion of the drug were measured. Intravenous bolus injection of the drug in dose of 10 mg/kg and 20 mg/kg yielded mean serum levels of 26.6 mcg/ml and 55.7 mcg/ml at 30 minutes, respectively. The serum levels of the drug, thereafter, declined gradually but still remained 1.3 mcg/ml and 2.7 mcg/ml at 6 hours. The serum half-lives (T 1/2) were estimated to be 1.17 hours in dose of 10 mg/kg and 1.31 hours in dose of 20 mg/kg. When a dose of 20 mg/kg was infused over a period of 30 minutes, the serum levels attained the peak of 72.4 mcg/ml to 82.4 mcg/ml (mean 79.4 mcg/ml) at the end of infusion. The levels, thereafter, tapered to mean levels of 45.3 mcg/ml at 30 minutes, 24.7 mcg/ml at 1 1/2 hours, and 3.6 mcg/ml at 5 1/2 hours, with a T 1/2 of 1.22 hours. Meanwhile, when the same dose was infused over 1 hour, the serum levels attained the peak of 59.4 mcg/ml to 68.5 mcg/ml (mean 64.2 mcg/ml). The mean serum levels after the end of infusion were 41.3 mcg/ml at 30 minutes, 21.6 mcg/ml at 1 hour and 1.9 mcg/ml at 5 hours, with a T 1/2 of 0.97 hours. Urinary recovery of the drug was 69.2% to 79.9% after intravenous injection and 62.3% to 79.9% after drip infusion, most of the given drug was excreted in the first 2 hours after administration. In our clinical study, 27 children with moderate or severe infections (12 cases of bronchopneumonia or bronchitis, 5 of pyelonephritis, 3 of purulent meningitis, etc.) were treated with ceftizoxime at the daily dose of 30--309 mg/kg for 3--23 days. Clinical response was excellent in 10, good in 9, fair in 5 and poor in 3. The drug was proved to be very effective against infections due to H. influenzae K. pneumoniae, E. coli and S. aureus. No serious side effects were observed in any case.     

Stability of amoxicillin in portable pumps is drug concentration dependent

Continuous amoxicillin infusion for deep infection's intravenous treatment is performed using elastomeric portable pumps carried under clothing and requires high doses of antibiotic. Therefore, we evaluated the stability of amoxicillin in those medical devices, with particular focus on both drug concentration and storage temperature. Stability of 20, 40, and 60g/L amoxicillin solutions in 300 mL portable pumps stored at 20 or 35 degrees C was studied by visual examination and drug concentration measurements at T0; T0 + 12 h; T0 + 24 h and; T0 + 48 h. Twenty and 40 g/L amoxicillin solutions were stable over 48 h, with a degradation rate that never exceeded 12% at T0 + 24 h, and 18% at T 0 + 48 h. However, the 60 g/L amoxicillin solution degradation rate was significant (p < 0.05, versus C1 and C2) at T0 + 24 h: 24.5 and 26.9% at 20 and 35 degrees C, respectively. This degradation process was amplified at T0 + 48 h, with degradation rates of 37 and 42% at 20 and 35 degrees C, respectively. Stability of amoxicillin in pump is guarantied over 48 h up to concentrations of 40 g/L. At 60 g/L major degradation of the antibiotic was observed.     

中国健康受试者多剂量静脉滴注左氧氟沙星注射液的药物动力学

目的:研究左氧氟沙星注射液多剂量给药在健康人体内的药代动力学.方法:10名健康男性受试者给予左氧氟沙星注射液200mg,注射时间为60min,连续给药7天,其中第1天及第7天给药1次,第2到6天每天给药2次,间隔12h 采用反相高效液相色谱法测定血及尿药浓度.结果:第一次给药的主要药物动力学参数:C_(max)(2.4±0.4)mg/L;AUC_(0-∞)(16.1±1.4)mg·h·L~(-1);T1/3β(6.3±0.3)h.血药浓度于第3天达稳态,稳态后最后一次给药的主要药物动力学参数:C_(ssmax)(2.9±0.4)mg/L;C_(ssmin)(0.71 0.19)mg/L;C_(av)(1.40±0.29)mg/L;AUC_(ss0-12)(17±3)mg·h·L~(-1),T1/2β(6.2±0.8)h.24h内平均尿累积排泄百分率为(88±5)％.累积比为1.20,波动系数为1.30.第一次给药与最后一次给药T1/2β及AUC差异无显著性(P>0.05).整个试验期间,受试者未出现明显的不良反应.结论:左氧氟沙星注射液200mg连续给药7天,药物在体内无明显蓄积.