健康者体内头孢唑林对阿米卡星药动学的影响

采用微量微生物法对阿米卡星（ＡＭＫ）单用及ＡＭＫ与头孢唑林（ＣＥＺ）合用后,健康者体内ＡＭＫ血药浓度进行测定;药时数据用ＭＣＰＫＰ软件经ＩＢＭ计算机处理,并对两组药动学参数进行了统计学处理,结果表明ＣＥＺ对ＡＭＫ的药动学有显著的影响。     

氨苄青霉素对丁胺卡那霉素药动学的影响

本文采用微量微生物法对ＡＭＫ单用及ＡＭＫ与ＡＭＰ合用后，兔体内ＡＭＫ血、尿药浓度进行测定；药时数据用ＭＣＰＫＰ软件经ＩＢＭ计算机处理，并对两组药动学参数进行了统计学处理。结果表明ＡＭＰ对ＡＭＫ的药动学有显著的影响。     

皮康霜中醋酸曲安奈德和硝酸咪康唑的HPLC测定

皮康霜中醋酸曲安奈德和硝酸咪康唑的ＨＰＬＣ测定刘伟（襄樊市药品检验所，湖北４４１０２１）ＨＰＬＣＤＥＴＥＲＭＩＮＡＴＩＯＮＯＦＴＲＩＡＭＣＩＮＯＬＯＮＥＡＣＥＴＯＮＩＤＥＡＣＥＴＡＴＥＡＮＤＭＩＣＯＮＡＺＯＬＥＮＩＴＲＡＴＥＩＮＰＩＫＡＮＧＳＨＵＡＮ...     

氯化钾泡腾颗粒的药代动力学研究

２０名健康自愿受试者分别于规定时间口服氟化钾泡腾颗粒（ＴＰＥＧ）和１０％氯化钾（ＫＣｌ）液，用原子吸收分光光度法测定血清Ｋ＋浓度，以二室模型拟合，在ＴＢＭ机上计算药动学参数。结果表明：实验组与对照组氯化钾的Ｋａ、ｔ（１／２）Ｋａ、α、ｔ（１／２）α、ＡＵＣ（０－∞）很接近，两者的Ｋ（２１）／Ｋ（１２）之比值分别为４．８５９和１．２２２，ＡＵＣ（０－∞）分别为１９７．１９０ｍｇ／ｍｌ·ｈ和２００．５８５ｍｇ／ｍｌ·ｈ，经ＳｔｕｄｅｎｔＴ检验无显著差异（ｐ＞０．０５），Ｆ＝９８．３％，证明ＴＰＥＧ有较好的补血钾效果。     

复方新诺明和甲氧等氨嘧啶对丁胺卡那霉素药代动力学的影响

本文利用ＦＰＩＡ法测定了家兔丁胺卡那霉素单用与ＳＭＺ－ＴＭＰ或ＴＭＰ合用时的药代动力学变化。结果测得单用时Ｋｅ＝０．０１０８±０．００１３ｍｉｎ＾－１，Ｔ１／２＝６５．８９±７．３０ｍｉｎ，ＡＵＣ＝０．２９０８±２７８．０３ｍｉｎ．μｇ／ｍｌ，Ｔｐｅａｋ＝２９．９４±１１．０６ｍｉｈ，ＣＬ／ｆ（ｓ）＝０．０００６７９０±０．０００１４６ｌ／ｋｇ．ｍｉｎ；（Ⅱ）与ＳＭＺ－ＴＭＰ合用时ＫＥ＝０．００９     

毛细管胶束电动色谱法测定内江猪血清中的安替比林

研究毛细管胶束电动色谱法（ Ｍ Ｅ Ｋ Ｃ）测定血清安替比林的方法。以对乙酰氨基酚为内标,采用 Ｍ Ｅ Ｋ Ｃ 技术,调节电泳缓冲液 ｐ Ｈ 和表面活性剂 Ｓ Ｄ Ｓ浓度,取得了最佳分离效果。最佳分析条件为５０ ｍ ｍ ｏｌ／ Ｌ硼酸硼酸钠缓冲液（含 ５０ ｍ ｍ ｏｌ／ Ｌ Ｓ Ｄ Ｓ,ｐ Ｈ ９０１）;毛细管内径 ７５ μｍ ,有效长度 ４０ ｃｍ ,毛细管温度 ２０℃,压力进样 １０ ｓ,电压 ２０ ｋ Ｖ,２５４ ｎｍ Ｕ Ｖ 检测。方法快速,电泳 ８ ｍ ｉｎ 即可完成对 Ａ Ｐ和 Ａ Ａ Ｐ 的有效分离和定量。在 ５～３２０ μｇ／ｍ ｌ范围内线性良好（ｒ＝ ０９９９９）。并研究了 Ａ Ｐ 在内江猪体内的药代动力学,血药浓度时间数据经 ３ Ｐ８７ 药动学软件处理得到药代动力学参数,发现内江猪对 Ａ Ｐ 的代谢为二室开放模型,消除半衰期为 ６２３５ ｍ ｉｎ,血浆清除率为 ５２ ｍ ｌ／（ｋｇ·ｍ ｉｎ）。     

美托洛尔光学异构体在犬体内的药动学-药效学结合模型

用麻醉犬研究美托洛尔（Ｍｅｔ）光学异构体药动学—药效学结合模型。结果表明，ｉｇ（＋）Ｍｅｔ或（－）Ｍｅｔ后，其药动学符合二室模型，药动学参数Ｖｄ／Ｆ，ＣＬｓ／Ｆ和ＡＵＣ在两种Ｍｅｔ之间有显著性差异。（＋）Ｍｅｔ和（－）Ｍｅｔ的效应和血药浓度关系呈逆时针滞后环。引入效应室理论后，药效和效应室浓度之间的关系符合ＳｉｇｍｏｉｄＥｍａｘ模型。应用ＣＡＰＰ软件进行模型拟合，血药浓度的预测值和药效的预测值皆与其实测值较为接近。（＋）Ｍｅｔ抑制Ｖｍａｘ，ｄｐ／ｄｔｍａｘ及ＨＲ效应的Ｃｅ５０分别是（－）Ｍｅｔ的３７，６８，６３倍，证实（－）Ｍｅｔ对犬心脏的抑制作用强于（＋）Ｍｅｔ。     

22种抗生素对铜绿假单胞菌抑菌浓度研究

用ＡＭＳ法测定了２２种抗生素对铜绿假单胞菌临床菌株的抑菌浓度。ＣＰＬＸ对铜绿假单胞菌的抑菌浓度为０．６４ｍ ｇ／Ｌ,ＴＯＢ、ＩＭＰ、ＧＭ 和ＡＭＫ为１．９５～７．７３ｍｇ／Ｌ,ＣＡＺ、ＡＺ、ＣＰＺ、ＴＣ、ＰＩＰＣ、ＣＴＸ、ＣＥＺ、ＣＸＭ－Ｓ、ＣＸＭ－Ａ、ＣＥＴ和ＡＢＰＣ为９．４１～３２．００ｍｇ／Ｌ,ＣＦＸ、ＴＩＰＣ、ＴＩＰＣ／ＣＡ、ＭＺＰＣ和ＣＢＰＣ为３３．９８～１００．３０ｍ ｇ／Ｌ,ＮＦＴ为１９３．００ｍ ｇ／Ｌ。在不同标本的分离菌中,痰液与伤口、痰液与粪便和伤口与尿液有４种抗生素、痰液与尿液和伤口与粪便有５ 种抗生素、粪便与尿液有１１ 种抗生素的抑菌浓度有显著性差异（Ｐ＜０．０５０～０．００１）。     

头孢唑啉钠和头孢哌酮钠结晶的制备

头孢唑啉钠和头孢哌酮钠结晶的制备ＰＲＥＰＡＲＡＴＩＯＮＯＦＣＲＹＳＴＡＬＬＩＮＥＣＥＰＨＡＺＯＬＩＮＳＯＤＩＵＭＡＮＤＣＥＦＯＰＥＲＡＺＯＮＥＳＯＤＩＵＭ万平＊黄敏康刘丹青刘红英田美茹（白云山制药股份有限公司，广州５１０５１５）ＷＡＮＰｉｎｇ＊，ＨＵ...     

饮食对正常人口服林可霉素溶液剂药代动力学的影响

饮食对正常人口服林可霉素溶液剂药代动力学的影响周森磷，沈刚，谭明（上海医科大学儿科医院药剂科，附属眼、耳、鼻、喉、医院，上海２０００３２）ＤＩＥＴＡＲＹＥＦＦＥＣＴＯＮＰＨＡＲＭＡＣＯＫＩＮＥＴＩＣＳＯＦＯＲＡＬＬＩＮＣＯＭＹＣＩＮＳＯＬＵＴＩＯＮＩ...     

Studies on protein binding of antibiotics. II. Effect of apalcillin on protein binding and pharmacokinetics of cefoperazone and cefazolin

The drug-protein interactions between cefoperazone (CPZ) and apalcillin (APPC), and between cefazolin (CEZ) and APPC were investigated in in vitro and in vivo experiments. Through the binding rates of CPZ or CEZ to rabbit serum and human serum albumin subsided remarkably with increased drug concentrations, APPC was not greatly affected, even at high concentrations. It appeared that APPC had a higher binding capacity to protein than CPZ or CEZ. From the results of competitive study, it became clear that APPC partially shared the binding sites on protein with CPZ or CEZ. The CPZ or CEZ serum levels in rabbits administered together with APPC were not different from those for the single administration, but APPC levels for the simultaneous administration were slightly lower.     

Pharmacokinetic studies on the concomitant administration of piperacillin and cefazolin, and piperacillin and cefoperazone in rabbits

The pharmacokinetics of each drug on the concomitant administration of piperacillin (PIPC) and cefazolin (CEZ) or cefoperazone (CPZ) were studied in rabbits. When rabbits received the consecutive drip infusion administration of CEZ (0.71 mg/kg/minute) and PIPC (1.38 mg/kg/minute) and likewise of CPZ (0.72 mg/kg/minute) and PIPC (1.54 mg/kg/minute) for 1 hour, respectively, the serum half-lives of CEZ and CPZ were respectively prolonged about 1.8 and 1.6 times during drip infusion of PIPC than administered alone. However, when the sequence of administration were reversed, the serum levels of PIPC were not affected by the consecutive drip infusion administration of CEZ and CPZ. To study these findings in detail, the single intravenous dose of 20 mg/kg of CEZ and CPZ were administered under drip infusion of PIPC (2.65-2.93 mg/kg/minute). The serum half-lives of CEZ and CPZ were also prolonged about 5.4 and 1.9 times, respectively, whereas urinary excretion of CEZ, and urinary and biliary excretion of CPZ were reduced by PIPC. Moreover, when the single intravenous dose of 20 mg/kg of PIPC were administered under drip infusion administration of CEZ (0.96-2.60 2.60 mg/kg/minute), the pharmacokinetics of PIPC was not affected by the presence of CEZ. However, under drip infusion administration of CPZ (2.60-2.70 mg/kg/minute), the PIPC serum half-life was prolonged about 1.4 times, and biliary excretion of PIPC was reduced but urinary excretion was not. From the results of renal clearance experiments, tubular secretion appeared to be the predominant mechanism of renal elimination for these three drugs. These results indicate that PIPC influences the pharmacokinetics of both drugs by the competitively inhibiting tubular secretion in CEZ, and tubular secretion and hepatic transport system in CPZ. Therefore, in this respect PIPC seems to have probenecid-like action.     

Muscle irritation study on cefoperazone (author's transl)

Muscular injury caused by cefoperazone (CPZ) was compared with that of cefazolin (CEZ), cephaloridine (CER) or cephalothin (CET) in adult and juvenile male rabbits. These drugs were dissolved by the way of clinical use and were injected singly into the muscular vastus lateralis. Then, the degree of muscular injury at the time of 48 hours and 7 days after the injection was judged from muscle ratio, gross local observation and histological observations. The degree of muscular injury caused by these drugs was compared also with that of saline 075% or 6% acetic acid. The following results were obtained: There was no difference among CPZ, CEZ and CER on the degree of muscular injury and these changes were almost equal to those of 0.75% acetic acid, however severer than that of saline. While, muscular injury caused by CET was severer than that of CPZ, CEZ, CER or 0.75% acetic acid, but milder than 6% acetic acid. The inflammatory reaction against these drugs was almost similar in adult and juvenile rabbits.     

Comparative nephrotoxicity of latamoxef and other cephalosporins in rabbits. Combined administration with furosemide or tobramycin. (author's transl)

I. The nephrotoxic potential of latamoxef (LMOX, 6059-S) was evaluated in male rabbits after combined administration of 500 or 2,000 mg/kg of the compound (ear vein) with subcutaneous injection of furosemide (FUR) at 50 mg/kg. Histological examination of kidney tissues of all animals were performed after 72 hours. Three rabbits were used at each dose level, and comparative studies were performed using several cephalosporins, such as CET and CEZ. Neither LMOX nor CET produced nephrotoxic effects at 500 mg/kg when given in combination with FUR. Although slight elevation of BUN and creatinine in plasma and hyaline casts in lumen of the distal tubules were observed in animals receiving 2,000 mg/kg of LMOX or CET when dosed with FUR, no histological changes were found in renal tissues. Significantly more nephrotoxicity was observed with the treatment of CEZ alone, and this toxicity was augmented in combination with FUR. II. Concomitant administration of LMOX with intramuscular injection of tobramycin (TOB) was estimated in male rabbits. Rabbits received daily intramuscular injection of TOB at 50 mg/kg for 10 days in combination with single dosing of LMOX (500 or 2,000 mg/kg) on the 8th day after the start of TOB treatment. Three rabbits were used at each dose level, and comparative studies were conducted using CET or CEZ. All rabbits were killed 48 hours after the last injection of TOB and examined histopathologically. Combined administrations of LMOX or CET did not aggravate the nephrotoxicity induced by TOB. However, CEZ enhanced renal injuries produced by TOB injection.     

不同给药途径对家兔阿米卡星药动学参数的影响

目的 :研究肌注和鼻甲注射对家兔阿米卡星 (AMK)药动学参数的影响。方法 :8只家兔予AMK 4mg·kg-1,im ,2wk后再以鼻甲注射同等剂量的AMK ,分别于给药后不同的时间点取血。通过荧光偏振免疫法 ,测定AMK的血药浓度 ,获得不同的药动学参数。结果 :肌注和鼻甲注射AMK后 ,Ke ,cmax和AUC均无显著性差异 ,而Ka ,T1/2 (Ka) ,tmax均有显著差异 (P <0 0 0 1) ;但鼻甲注射方法的达峰浓度较肌注高。结论 :鼻甲注射AMK后吸收较肌注迅速 ,两者的消除相似     

Study on the drug sensitivity of multiple drug-resistant Staphylococcus aureus

Of clinically isolated Staphylococcus aureus showing resistance to multiple drugs among penicillins (PCs), cephem antibiotics (CEPs), aminoglycosides (AGs), minocycline (MINO) and fosfomycin (FOM), 64 strains were selected for the determination of MIC. Twenty-one drugs were used for the determination of MIC, with ampicillin (ABPC), cloxacillin (MCIPC), cephalothin (CET), cefazolin (CEZ), cefotiam (CTM), cefuroxime (CXM), cefamandole (CMD), cefotaxime (CTX), ceftizoxime (CZX), cefmenoxime (CMX), cefmetazole (CMZ), cefoxitin (CFX), latamoxef (LMOX), cefotetan (CTT), cefoperazone (CPZ), gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), MINO, and FOM. MIC80 of each drug at 10(6) CFU/ml were: ABPC, MCIPC, CEZ, CTM, CXM, CTX, CZX, CMX, CFX, LMOX, CTT, CPZ, GM, DKB and TOB greater than 100 micrograms/ml; CET 50 micrograms/ml; CMD and AMK 25 micrograms/ml; CMZ 12.5 micrograms/ml; FOM 6.25 micrograms/ml; and MINO 0.78 micrograms/ml. The ratio of highly resistant strains with MIC greater than 100 micrograms/ml at 10(6) CFU/ml varied according to drug, and a difference tended to be seen in the degree of influence by resistant factors reflected upon MIC, e.g. drugs for which a high resistance of more than 50% was confirmed were ABPC, CXM, CZX, LMOX and TOB, and 20 approximately 30% MCIPC, CTM, CTX, CMX and CFX. MIC on MCIPC which has a correlation of structural activity with methicillin correlated with cephems (CEPs) resistance to a high degree, but many of the so-called new CEPs showed resistance even to the strains with a low MIC on MCIPC. It was assumed that CEPs resistant strains have multiple drug resistant factors based on the fact that such strains showed multiple drug resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Investigation on the use of amikacin in the newborn

The use of amikacin (AMK) in newborns was investigated and the results obtained are summarized as follows. 1. AMK was administered to 3 rabbits at an intramuscular dose of 6 mg/kg. Mean blood levels determined according to methods of bioassay (BIO) and fluorescent immunoassay (FIA) were 28.6 and 22.2 micrograms/ml, respectively, at 30 minutes after dosing. Then, the blood levels declined rapidly. Mean T 1/2 values obtained with the above 2 assay methods were 0.76 and 0.63 hours, respectively. 2. When AMK was administered at a dose of 5.7 mg/kg to a 64 day-old newborn by drip intravenous infusion for 30 minutes, a peak blood level was attained at the end of drip intravenous infusion, which was 20.0 micrograms/ml according to BIO and was 15.5 micrograms/ml according to FIA. The blood levels declined gradually thereafter with a T 1/2 value of 2.33 hours (BIO) or 2.03 hours (FIA). When the drug was administered at 5.3 mg/kg to a 26 day-old newborn using the same infusion method, the peak blood level obtained at the end of drip intravenous infusion was 18.0 micrograms/ml according to BIO and was 14.8 micrograms/ml according to FIA, and T 1/2 values were 4.76 and 3.68 hours, respectively. 3. As there was a close correlation between the values obtained with BIO and with FIA in both rabbits and clinical cases, with a coefficient of 0.990, and also the BIO values could be estimated using a formula of FIA value X 1.2 + 2.2, it would be possible to monitor AMK levels in the blood of patients at bedside using the FIA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antibacterial activities of various aminoglycosides against clinically isolated methicillin-resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus (MRSA) were isolated from samples collected from various patients during 1986, and antibacterial activities of 6 aminoglycosides (AGs) (netilmicin (NTL), gentamicin (GM), sisomicin (SISO), dibekacin (DKB), tobramycin (TOB) and amikacin (AMK] and 4 beta-lactam antibiotics (cefazolin (CEZ), cefmetazole (CMZ), cloxacillin (MCIPC) and methicillin (DMPPC) against these MRSA were evaluated. Among these 6 AGs, NTL was the most potent, and its MIC50 and MIC80 were 1.56 and 3.13 micrograms/ml, respectively. Antibacterial activities of GM, SISO, DKB and TOB were weak, and MIC50's of GM and DKB were both 100 micrograms/ml, while those of SISO and TOB were 50 and greater than 100 micrograms/ml, respectively. Frequency of highly resistant specimens to AMK was rather low and its MIC50 and MIC80 were 12.5 and 25 micrograms/ml, respectively. As for antibacterial activities of the above 4 beta-lactam antibiotics, the MIC50 and MIC80 of CMZ were 6.25 and 12.5 micrograms/ml, respectively, and therefore, its antibacterial activity to MRSA is relatively good. However, MIC50's of CEZ, MCIPC and DMPPC were all greater than 100 micrograms/ml, showing poor antibacterial activities. Recently, MRSA became a problem in various fields of clinical practice, and a number of literatures reporting refractory infections caused by MRSA have been published. Since MRSA is featured as multiply resistant bacteria, it is known that MRSA is resistant to the majority of existing antibiotics (penicillins, cephems, macrolides, AGs, etc.). In 1985, we reported results of our study concerning the antibacterial activities of a number of CEPs and some of AGs against multiply resistant S. aureus including MRSA.(ABSTRACT TRUNCATED AT 250 WORDS)