头孢唑林对阿米卡星在兔体内的药动学影响

采用微量微生物法对阿米卡星（ＡＭＫ）单用及与头孢唑林（ＣＥＺ）合用后兔体内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...     

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     

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。     

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。     

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）。     

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...     

汉防己甲素对环孢素A药物动力学参数的影响

目的：汉防己甲素对环孢素Ａ药物动力学参数的影响。方法：采用荧光偏振免疫分析法（ＦＰＩＡ）对单用环孢素Ａ（ＣｓＡ）及ＣｓＡ与汉防己甲素（Ｔｅｔ）合用后，家兔体内ＣｓＡ全血药物浓度进行了测定，并对两组药动学参数进行了统计学处理。结果：Ｔｅｔ可使ＣｓＡ的ＡＵＣ略有增大，合并给药组与对照组比较Ｃｍａｘ差异有显著性（Ｐ＜０．０５），其余药动学参数无显著变化。结论：ＣｓＡ与Ｔｅｔ合用可行，并可减轻ＣｓＡ的毒副作用     

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）。     

阿米卡星在老年呼吸系统感染患者体内的药动学研究

目的 :研究阿米卡星 (AMK)在老年呼吸系统感染患者体内的药动学 ,为临床合理用药提供依据。方法 :用荧光偏振免疫方法测定药物的血药浓度。结果 :AMK的药 -时曲线符合二房室模型。AMK在健康志愿者和老年呼吸系统感染患者体内的T1/2β 分别为 (2 14±0 81)h、(4 32±1 05)h ;AUC分别为 (70 68±26 47) (mg·h)/L、(101 83±9 73) (mg·h)/L。结论 :AMK在老年呼吸系统感染患者体内的药动学过程与健康志愿者之间呈现显著性差异     

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)     

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)     

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.     

Bacterial species recently isolated from urinary tract infections and their antibiotic susceptibility, with special reference to acute cystitis

Numbers of the strains of each bacterial species isolated from urinary tract infections were summed and their incidences were calculated for each a half year from the second half of 1980 to the first half of 1982. The incidences of Escherichia coli strains were found to be greatly reduced and those of Streptococcus faecalis strains were greatly increased. Those of Staphylococcus epidermidis strains were also increased. This trend was thought to be caused by the extensive and exclusive use of cephalosporin derivatives. Minimal inhibitory concentrations of gentamicin (GM), amikacin (AMK), ampicillin (ABPC), cefazolin (CEZ), ceftizoxime (CZX), latamoxef (LMOX) and minocycline (MINO) against these isolated strains were estimated. The most sensitive drugs for E. coli were found to be CZX, LMOX, GM and AMK, CZX and MINO for Klebsiella, CZX and LMOX for Proteus, and GM for Pseudomonas aeruginosa. All Gram-positive cocci were found generally to be most susceptible to MINO, but S. faecalis and other Pseudomonas were also sensitive to ABPC. Exclusive use of cephalosporins for the treatment may induce selective increases of the resistant species in normal flora. Since these flora could be the causative agents for various infections, these selections caused by the exclusive use of the monotype drugs are not preferable, and various different drugs should be used for the suitable cases.     

Effect of Experimental Renal Failure and Hypotonic Hyponatremia on the Pharmacodynamics of Cefazolin-Induced Seizures in Rats

Purpose. The purpose of this study was to investigate the effect of experimental renal failure and hypotonic hyponatremia on the pharmacodynamics of cefazolin (CEZ)-induced seizures. Methods. Rats received an intravenous infusion of CEZ until the onset of seizures. Renal failure was produced by bilateral ureteral ligation (UL) or uranyl nitrate (UN) injection. Hypotonic hyponatremia was produced by intravenous infusion of 5% dextrose in water or intraperitoneal infusion of distilled water after arginine vasopressin injection. Results. The serum and brain concentrations of CEZ at the onset of seizures increased with increasing infusion rate, but the CSF concentration of CEZ at the onset of seizures was not affected by the infusion rate. The concentration of CEZ in CSF at the onset of seizures was significantly lower in UL rats than control rats, whereas there was no difference between UN rats and their controls. Serum concentrations of Na⁺ and serum tonicity were lower in UL rats than UN rats. Hypotonic hyponatremia had no apparent effect on the CSF concentration of CEZ. The CSF concentration of CEZ at the onset of seizures was significantly lower in UN rats with hypotonic hyponatremia than their controls. Conclusions. Renal failure with severe hypotonic hyponatremia is associated with increased central nervous system sensitivity to CEZ-induced seizures.     

Effect of isoniazid on the pharmacodynamics of cefazolin-induced seizures in rats

Both isoniazid (INH) and cefazolin (CEZ) can have serious adverse effects on the central nervous system (CNS), causing seizures. In this study, we investigated the effect of INH on the pharmacodynamics of CEZ-induced seizures in rats. Male Wistar rats pretreated with INH (150 mg/kg i.p.) or saline received an intravenous infusion of CEZ at 3.2 g/h/rat until the onset of seizures, then samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained immediately. The administration of INH was associated with a reduction in the total dose of CEZ required to produce seizures. The concentrations of CEZ in serum, brain, and CSF in INH-treated rats at the onset of seizures were significantly lower than those in control rats. In rats coadministered with pyridoxine (150 mg/kg s.c.), the concentration of CEZ in CSF at the onset of seizures was significantly higher than that in rats administered INH only. These results suggest that INH potentiates the sensitivity of the CNS to CEZ-induced seizures, and that the increased sensitivity is associated with the inhibition of vitamin B(6) metabolism by INH.     

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.