冰片和川芎嗪血药浓度的GC-MSD测定法

建立了用气相色谱—质谱检测法同时测定血浆中冰片和川芎嗪血药浓度的方法。冰片和川芎嗪浓度在10～300ng/ml范围内线性关系良好。冰片和川芎嗪的血中回收率分别为97.32%和87.37%;最低检测浓度为2ng/ml。本方法以樟脑为内标,SIM方式检测,定量准确、干扰小,日内及日间的相对标准偏差分别小于4%和7%。并应用本法成功地进行了动物实验和健康人含服速效救心丸后冰片的药代动力学研究。     

高效液相色谱法测定炎痛喜康血药浓度及人体药物动力学参数

本文建立了用高效液相色谱法测定人体内炎痛喜康血药浓度的分析方法,以YWG-C₁₈化学键合相(10μm)为固定相,以0.2 M醋酸铵—甲醇(1:1 Ⅴ/Ⅴ)为流动相,非那西汀为内标,使用国产HPLC仪,UV 254 nm检测器,得出检出限为5 ng,最低检测浓度为0.05μg/ml血清,线性范围为0.1～10μg/ml,方法回收率为99.28%。本法简便、重现性好、专一性强。健康志愿者口服炎痛喜康20 mg一片后,用本法测定得到的药动学参数与文献报道值接近。     

利多卡因燐光分析法及其在药物动力学上的应用

利多卡因在pH3.4时能与金莲橙OOⅣ结合成复合物并溶于氯仿中,将提取的复合物还原,测还原金莲橙燐光,由此计算利多卡因的含量。本法可检测3ng利多卡因,用于血中利多卡因测定,重复性较好,可定量回收。 小鼠im(10mg/kg),狗iv(4mg/kg)利多卡因后,测血药浓度,经药物动力学分析为二室型,其血药浓度表达式为:小鼠:C_((μg/ml))=2.49e~(-0.00677t)+3.43e~(-0.0217t -7.14e~(-0.0892t)。犬:C((μg/ml))=2.03e~(-0.0142t)+2.68e~(-0.146t)     

高效液相色谱法测定普罗帕酮血浆浓度

本文建立了高效液相色谱法测定人体内普罗帕酮血浆浓度。以YWG-C_(18)(10μm)为固定相,改性甲醇-乙腈-醋酸盐缓冲液(45.5:19.5:35)为流动相,用达克罗宁作内标在254nm波长处定量测定。方法最低检测限为5ng(S/W=3),血浆中最低检测浓度为25ng/ml,普罗帕酮血浆浓度在50～500ng/ml范围内线性关系良好,方法回收率为100.5％,不同浓度水平测定蛄果的日内和日间变异系数均小于3％。方法重现性好,专一性强,内源性物质不干扰,操作简便,快速,能适合梏床血药浓度监测及药代动力学研究。     

固相萃取高效液相色谱法测定人血浆中的沙丁胺醇

建立了固相萃取高效液相色谱法测定沙丁胺醇血药浓度的方法。采用LunaC18(5μm)分析柱，流动相为乙腈-水-磷酸-二乙胺(10900.150.25)，吗啡为内标，检测器激发波长278nm，发射波长314nm。本法平均回收率104.0％士4.1％，日内及日间相对标准偏差小于5.9％，血药浓度在0.5～35ng/ml呈线性关系，相关系数为0.9993，最低检测浓度为0.5ng/ml。     

178例次地高辛血药浓度监测分析

对 1 41例服用地高辛的充血性心衰患者进行了 1 78例次血药浓度测定 ,结果表明该组中以老年患者为主 (93.6% ) ,药物浓度多为 0 .8～ 1 .3ng/ml(62 .9% )和 0 .5～ 0 .8ng/ml(2 1 .3% ) ,给药方案以1 2 5μg,qd居多 (72 .5% ) ,多数病人疗效满意     

西罗莫司不同血药浓度对肾移植患者肝肾功能的影响

目的探讨西罗莫司不同血药浓度对肾移植患者肝肾功能的影响。方法 45例肾移植术后服用西罗莫司治疗的患者,采用高效液相色谱法(HPLC法)检测西罗莫司的血液浓度,比较分析不同血药浓度下肝肾指标的变化情况。结果西罗莫司血药浓度≤8 ng/ml组患者的天门冬氨酸肌转酶(AST)、丙氨酸氨基转移酶(ALT)、直接胆红素(DBIL)分别为(65.26±12.68)U/L、(70.19±13.66)U/L、(11.05±9.64)μmol/L,显著低于>8 ng/ml组,差异均具有统计学意义(P<0.05);西罗莫司血药浓度为4~8 ng/ml组患者的内生肌酐清除率(Ccr)为(82.64±17.32)ml/(min·70 kg),显著高于<4 ng/ml组、>8 ng/ml组,差异具有统计学意义(P<0.05)。结论肾移植术后采用西罗莫司行免疫抑制治疗时,血药浓度控制在4~8 ng/ml最佳。     

超高效液相色谱串联质谱法测定肾移植患者体内霉酚酸的血药浓度

目的:建立一种快速、准确测定肾移植患者体内霉酚酸血药浓度的方法。方法:肾移植患者的血样经处理后,采用超高效液相色谱串联质谱(UPLC-MS/MS)法进样测定。色谱柱为Acquity UPLC~ BEH-C18,流动相为0.01mol/L甲酸铵水溶液-甲醇(梯度洗脱);以电喷雾离子源(ESI)模式的多离子反应监测(MRM)扫描方式进行分析测定。结果:霉酚酸血药浓度在0.10～30.02μg/ml范围内线性关系良好(r=0.9945),最低检测限为0.01ng/ml;方法回收率为83.47%～99.20%,日内、日间RSD均<10%,稳定性试验RSD<10%。结论:本方法快速、准确、灵敏度高、专属性强,适用于肾移植患者体内霉酚酸的血药浓度监测。     

78例地戈辛血药浓度监测分析

目的　分析影响地戈辛血药浓度的因素。方法　应用荧光偏振免疫法 (FPIA)测定地戈辛血药浓度 ,有效血药浓度范围 0 .5～ 2 .0 ng/ m l[1 ]。结果　共监测 78例 ,<0 .5 ng/ ml的 14例 ,0 .5～ 2 ng/ ml范围内的 5 2例 ,>2 .0 ng/ ml的 12例。结论　影响地戈辛血药浓度的原因较复杂 ,临床上进行血药浓度监测很有必要     

罗格列酮在Beagle犬体内血药浓度测定方法研究

目的建立高效液相色谱法测定Beagle犬体内罗格列酮血药浓度的方法。方法以十八烷基键合硅胶柱为固定相,以0.01mol/L的磷酸二氢钾水溶液-乙腈(50∶50),以三乙胺调节pH6.0为流动相,检测波长247nm。4-硝基-2-苯氧基甲烷磺酰苯胺为内标,样品用乙醚提取,按内标法定量。结果标准曲线50~5000ng/ml范围内有良好线性关系(r=0.9996),最低检测浓度为30ng/ml,平均方法回收率为97.34%(RSD为2.15%)。结论本文建立的方法能够准确测定罗格列酮的血药浓度,线性关系好,回收率高,稳定耐用。     

The pharmacology of orally administered ciprofloxacin

Ciprofloxacin pharmacokinetics were studied in 6 volunteers after 250 and 500 mg single oral doses. Mean peak serum levels were 1.45 micrograms/ml and 2.5 micrograms/ml for 250 and 500 mg doses. The 12-h levels were 0.12 micrograms and 0.22 micrograms. T1/2 alpha values were 0.32 and 0.43 h; T1/2 beta was 4 h and Vd (area) values were 80L and 90L for the two doses respectively. AUC was 5.65 h. micrograms/ml and 10.37 h. micrograms/ml. Serum clearance was 23L for both doses. Approximately 49% of the 250 mg dose and 43% of the 500 mg dose was recovered in the urine. Ciprofloxacin's in vitro activity and human pharmacology should permit a twice or once-daily dosing schedule for systemic infections due to most Enterobacteriaceae, Haemophilus, Branhamella and Pseudomonas and S. aureus, and once-daily doses for urinary and gastrointestinal infections.     

Comparative pharmacokinetic profiles of cinoxacin and pipemidic acid in humans

Serum and urinary levels of Cinoxacin and pipemidic acid were determined at 7-day intervals in the same 10 healthy volunteers after a single oral dose of respectively 500 and 400 mg of the drugs. Comparison of results shows that Cinoxacin was absorbed faster (absorption half-life, ta 1/2cin = 0.25 h) than pipemidic acid (ta 1/2pip = 0.37 h) and distributed in a smaller apparent volume (AVDcin = 23.5 1/1.73 m2; AVDpip = 60.1 1/1.73 m2). Biological half-lives were identical (tb 1/2cin = 2.10 h; tb 1/2pip = 2.15 h). On the other hand, serum levels for Cinoxacin at 1, 2 and 4 hours (8.1 +/- 1.5 micrograms/ml, 10.6 +/- 1.5 micrograms/ml, 5.6 +/- 1.3 micrograms/ml respectively) were higher than those for pipemidic acid (3.3 +/- 0.3 micrograms/ml, 3.4 +/- 0.5 micrograms/ml, 2.1 +/- 0.5 micrograms/ml respectively). Urinary excretion of the two derivatives during the 12 hours following their administration was similar (Ucin0-12h = 86%; Upip0-12h = 83%). Mean urinary concentrations were particularly high, still attaining respectively 90 +/- 29 micrograms/ml and 131 +/- 38 micrograms/ml in samples collected between the 9th and the 12th hours; these levels were well above the M.I.C. for the Gram-negative organisms included within the spectrum of activity of these two quinolones. In addition, predictive calculations of serum levels reached after multiple dosing indicate that at an administration rate of 500 mg every 6 or preferably every 4 hours, Cinoxacin concentrations should be sufficiently high to be of interest in the treatment of systemic infections by sensitive organisms.     

Pharmacokinetics of dactimicin in rats

Dactimicin is a new pseudo-disaccharidic aminoglycosidic antibiotic produced by Dactylosporangium matsuzakiense. The aim of the present research was to evaluate the pharmacokinetics of dactimicin intramuscularly administered, at the dosage of 20 mg/kg, in male Sprague-Dawley rats with an average b.w. of 200-220 g. Dactimicin levels were assessed by using a microbiological method (agar diffusion) employing Bacillus subtilis ATCC 6633 as test organism. Samples were collected immediately before and 0.25, 0.50, 1, 1.15 and 2 h after drug administration. The mean peak serum level, reached after 15 min, was 33.6 micrograms/ml (range 30.3-40 micrograms/ml); T1/2 beta was 0.42 h; extrapolated AUC was 26.8 mg h/l.     

Penetration of cefbuperazone, a new cephamycin antibiotic, into human peritoneal exudate

Pharmacokinetic studies were carried out on cefbuperazone ( CBPZ ) in 9 patients undergoing postoperative drainage. The concentration of CBPZ in serum and peritoneal exudate after one shot intravenous administration of 1 g was measured by bioassay and calculated respectively by two- and one-compartment open model. The results obtained were as follows: The pharmacokinetic parameters calculated from the serum levels were compared to those reported previously; T1/2 = 101 min., Vd = 4.06 L and Cl = 76 ml/min. The simulation curve of the peritoneal exudate level fit fairly with the mean values of 6 patients. It appeared that CBPZ penetrated somewhat slowly into peritoneal exudate with the peak value of 27.05 micrograms/ml at about 1 hour after the administration. The exudate levels thereafter declined more slowly than the serum ones (T1/2 = 134 min.). IT was 6.2 micrograms/ml even at 6 hours after the administration.     

Pharmacokinetic and clinical studies of clarithromycin in the pediatric field

Pharmacokinetic and clinical studies on clarithromycin (TE-031, A-56268), a new macrolide antibiotic, were performed in the pediatric field. 1. Pharmacokinetic investigation We studied serum concentrations and urinary excretions after single oral administration of TE-031 granules and tablets. Doses were 1, 5, 10 and 15 mg/kg body weight in case of granules (10% TE-031) and 150 mg/kg body weight in case of tablets (50 mg TE-031, 3 tablets). As results, Tmax's were 1-2 hours after administration in case of both granules and tablets. Cmax's in cases of granules were 0.29 +/- 0.15 micrograms/ml in 1 mg/kg administration, 2.53 +/- 0.71 micrograms/ml in 5 mg/kg, 4.11 +/- 1.37 micrograms/ml in 10 mg/kg, 6.28 +/- 1.48 micrograms/ml in 15 mg/kg showing a dose dependency. T 1/2's were 1.8-6.5 hours in cases of 1, 5, 10, 15 mg/kg of granules and tablets. T 1/2's became longer with increased doses. Urinary recoveries were 9.4 +/- 2.4% to 31.6 +/- 19.0% in 6 hours after administration. 2. Clinical investigation Clinical study was carried out in 24 patients of respiratory infections. Clinical efficacies were excellent in 11 patients, good in 12 patients and fair in 1 patient. The clinical efficacy rate was 95.8%. No side effects were observed. The above results suggest that TE-031 is a useful oral antibiotic for treating pediatric respiratory infections, especially those due to Mycoplasma pneumoniae.     

Pharmacokinetics of bisoprolol during repeated oral administration to healthy volunteers and patients with kidney or liver disease

The pharmacokinetics of bisoprolol were investigated following oral administration of 10mg once daily for 7 days in 8 healthy subjects, in 14 patients with different degrees of renal impairment and in 18 patients with liver disease. In healthy subjects peak and trough steady-state concentrations of 52 micrograms/L and 11 micrograms/L, respectively, an elimination half-life of 10.0 hours and total body clearance of 14.2 L/h were observed. 5.21 mg/24 hours of unchanged bisoprolol were recovered following urinary excretion during the dosage interval. In 11 patients with renal impairment (mean CLCR = 28 +/- 5 ml/min/1.72m2) half-life was prolonged to 18.5 hours, and peak and trough concentrations were 74 and 32 micrograms/L, respectively. Correspondingly, urinary excretion decreased to 3.35 mg/24 hours and total body clearance to 7.8 L/h. In uraemic patients (CLCR less than 5 ml/min/1.73m2) the total clearance of bisoprolol was 5.0 L/h and the elimination half-life was 24.2 hours. In patients with liver cirrhosis half-life increased to 13.5 hours, steady-state peak and trough concentrations increased to 62 and 22 micrograms/L, respectively, and total body clearance decreased to 10.8 L/h. The present study indicates that in patients with impairment of kidney or liver function accumulation of bisoprolol above a factor of 2 did not occur. However, in the terminal stages of insufficiency of kidney or liver function bisoprolol dosage should not exceed 10mg.     

Clinical studies of intravenous drip infusion of micronomicin. 1. Absorption and excretion

Pharmacokinetics of MCR administered by 1 hour intravenous drip infusion were studied in healthy volunteers by two-compartment model. In 120 mg-dosage group (n = 3) studies were made by single administration, and in 60 mg-dosage group (n = 4) were administered twice daily and continued until a total of 9 doses. Results: When MCR was administered in a 60 mg dosage, its Cmax was 4.3 +/- 0.3 micrograms/ml (mean +/- S.D.) after the 1st dose and 3.7 +/- 0.4 micrograms/ml after the 9th dose, while it was 8.8 +/- 1.0 micrograms/ml when the dosage was 120 mg. It should be noted that in the case of repeated dosing with 60 mg, serum levels just before administration were always below the analytical limit. The mean of T 1/2 was 1.69 +/- 0.14 hours, remaining stable at all determination. The kinetic parameters that showed different values between determinations performed after the 1st and 9th 60 mg doses were V1 (0.107 vs 0.164 L/kg) and Kel (1.02 vs 0.68 hr-1). This was also the case with comparison of 2 different dosage groups (60 mg 1st vs 120 mg; V1: 0.107 vs 0.135 L/kg, Kel: 1.02 vs 0.72 hr-1). There was no evidence indicative of side effect of MCR. Discussion: The above results demonstrated that Cmax and other kinetic parameters were little influenced by whether MCR was administered by intravenous drip infusion or by intramuscular injection. There was a little larger difference in AUC between those 2 routes of administration but the differences seemed negligible when the same dosage was used. Pharmacokinetic studies are to be continued in subjects whose renal function is impaired in different ways to establish the optimum dosage regimen for MCR.     

Clinical study on imipenem/cilastatin sodium in the field of pediatrics

Imipenem/cilastatin sodium (MK-0787/MK-0791) was administered to pediatric patients with infections, and the following results were obtained. Pharmacokinetic study Two children, 11 years of age (38 kg body weight) and 3 years of age (15.5 kg body weight), were administered by 30 minutes intravenous drip infusion a single dose of 500 mg/500 mg (13.2 mg/13.2 mg per kg) and 250 mg/250 mg (16.1 mg/16.1 mg per kg) of MK-0787/MK-0791, respectively. Serum concentrations of MK-0787 reached their peaks at the end of drip infusion at a value of 56.33 micrograms/ml and 55.98 micrograms/ml, respectively. Concentrations of the drug decreased as the time after the administration increased, and they reached 0.14 microgram/ml and 0.12 microgram/ml, respectively in the older and the younger children at 6 hours after the administration. Half-lives (T 1/2) of the drug in serum were calculated to be 1.21 hours and 1.04 hours, respectively. The concentration of the drug in cerebrospinal fluid for the 11 years old was 0.52 microgram/ml 2 hours after the drip infusion and the serum concentration at the time was 4.02 micrograms/ml. Peak serum concentrations of MK-0791 in the 2 children were 53.73 micrograms/ml and 22.99 micrograms/ml, respectively, at the end of drip infusion. After 1 hour, the serum concentration of the drug decreased to 10.54 micrograms/ml in 1 case and not detectable in the other case. Urinary recovery rates of MK-0787 in 6 hours after the drip infusion was 82.9% and 63.6% in the 2 children and those of MK-0791 were 57.9% and 74.6%. Clinical study Clinical studies on MK-0787/MK-0791 were carried out in 6 pediatric patients; 1 each with femoral cellulitis, sepsis suspected, salmonellosis, acute tonsillitis, bronchopneumonia and streptococcosis. Lengths of treatment were 2 2/3-4 days for 5 cases and 6 days for 1 case. The patients were treated by 30-60 minutes intravenous drip infusions twice a day for 1 case, and 3 times a day for 5 cases at daily doses of 54.5-66.7 mg/kg. The treatment was effective in all cases, with 3 cases judged excellent and 3 cases good. The safety of the drug was studied in 7 patients. No side effects nor clinically abnormal values were observed in any cases.     

The diffusion of cefazedone into heart muscle, prostatic and skin tissue and into bile

The diffusion of cefazedone into human heart muscle, prostatic and skin tissue as well as bile fluid was investigated. 40 to 80 min after a single injection of 100 mg/kg (n = 14) the concentration in the heart muscle was between 10.8 and 85.5 micrograms/g. The respective serum levels were between 117 and 168.1 micrograms/ml. The single i.v. injection of 2 g cefazedone resulted within 30 min in a mean concentration of 34.63 +/- 9.75 micrograms/g in the prostatic tissue and in serum levels of 139.07 +/- 39.68 micrograms/ml (n = 14). In 5 patients additional values were estimated after 60 min. At this time the antibiotic concentrations were 24.92 +/- 1.31 micrograms/g in the tissue, with simultaneous serum levels of 87.25 +/- 20.86 micrograms/ml. 1 h after a 500 mg i.v. dose, concentrations in bile taken from T-tube were between 71.4 and 210 micrograms/ml. After 2 h there was a mean level of 83.2 micrograms/ml which was significantly above the serum concentrations at the same time (1 h = 35.25 +/- 7.17; and 2 h = 20.5 micrograms/ml). The bile concentration of 2 patients taken 5 h after cefazedone injection was 4.95 and 11.6 micrograms/ml. The cefazedone concentrations in the skin were estimated mainly in biopsies from granulating leg ulcer tissues. The mean concentrations in 4 cases were 120 +/- 28.7 micrograms/g 3 h after i.v. injection of 2 g cefazedone. The simultaneous serum levels were between 14.85 and 68.2 micrograms/ml, in one patient with extreme venous stasis the tissue concentration was only 8.1 micrograms/g. Cefazedone should be regarded as an antibiotic with excellent penetration into tissues.