新氟喹诺酮类抗生素的不良反应

目的：综述新氟喹诺酮类抗生素的各种不良反应，为临床合理用药提供依据。方法：检索国内外文献，归纳有关新氟喹诺酮类抗生素不良反应报道。结果：新氟喹诺酮类抗生素耐受性好，最为常见的不良反应为胃肠道反应、中枢神经系统反应、变应性反应、光毒性和心血管毒性、肝毒性等。结论：新氟喹诺酮类抗生素虽然不良反应轻微，但仍应监测其不良反应。     

氟喹诺酮类药物对大鼠肝外组织GST、GR及GSH-Px活性的影响

目的探讨氟喹诺酮类药物对大鼠肺、脑、肾、小肠中谷胱甘肽S-转移酶、谷胱甘肽还原酶及谷胱甘肽过氧化物酶活性的影响。方法实验分为体外和体内两部份。从大鼠的肺、脑、肾、小肠制备S9,分别测定给予环丙沙星、妥氟沙星、司帕沙星前后三种谷胱甘肽相关酶的酶活性。结果体内实验和体外实验结果显示,三种药物对各组织的G ST活性较对照组均有不同程度的抑制(P<0.05),但体外实验与体内实验中各药物组与对照组的差异有所不同,且不同组织中G ST活性降低的程度也不同;药物组各组织的GR和G SH-Px活性较对照组有降低,但大多无显著性差异。结论氟喹诺酮类药物对肝外组织的G ST活性有一定的抑制作用,且对不同组织的G ST活性的抑制作用存在差别,对GR和G SH-Px活性有抑制的趋势。     

新氟喹诺酮类抗生素巴洛沙星研究进展

巴洛沙星(balofloxacin)是一种新型氟喹诺酮类抗生素,其对G-菌、G 菌均有优异的抗菌活性,对衣原体、支原体也有良好的作用,并具有较好的药动学性质.体内、体外试验均显示较低的毒性.对巴洛沙星的研究及应用情况进行了综述,主要涉及化学合成、药效学、药理学、毒理学、药动学和临床应用.     

氟喹诺酮类药物的光毒性

目的：介绍氟喹诺酮类药物的光毒性研究进展。方法：根据有关资料,总结氟喹诺酮类药物的光毒性机制及临床光毒性反应发生率。结果和结论：氟罗沙星和洛美沙星的光毒性反应发生率较高,临床应用该类药物应加以注意。     

志贺菌主动外排系统对氟喹诺酮类抗生素耐药性的影响

目的 探讨主动外排系统AcrAB-TolC在志贺菌对氟喹诺酮类抗生素耐药性中的作用.方法 K-B纸片扩散法及MIC测定2009-2011年天津地区临床分离的144株志贺菌的药敏情况;加入泵抑制剂CCCP(羰基氰氯苯腙)检测耐药菌株对氟喹诺类抗生素敏感性的变化;应用定量PCR研究外排泵基因acrAB-tolC表达以探讨外排泵在菌株对氟喹诺酮耐药中的作用.结果 144株志贺菌中,共有5株志贺菌对环丙沙星等氟喹诺酮类抗生素耐药,均为福氏志贺菌.加入泵抑制剂后,5株志贺菌对5种氟喹诺酮类抗生素的MIC下降了4～16倍,而对照菌株对上述药物的MIC没有变化或仅下降至原值的1/2.实时定量PCR结果表明耐药菌株外排泵基因acrA、acrB和tolC的mRNA水平显著高于敏感野生株(P＜0.05).结论 本地区志贺菌临床株对氟喹诺酮类抗生素环丙沙星及氧氟沙星耐药率最高,为3.47％.AcrAB-TolC外排泵基因的高表达是导致志贺菌对氟喹诺酮类抗生素耐药的主要原因之一.     

BONF对大鼠脑神经细胞损伤的保护作用

目的：建立体外培养大鼠脑神经细胞损伤模型,测定损伤前后不同时间LDH的水平,研究DBNF对脑皮质神经元的保护作用机制。方法：原代培养新生Witer大鼠的脑皮质神经细胞,建立体外脑神经损伤模型,通过测定神经细胞培养液中乳酸脱氢酶(LDH)的含量变化观察模型对神经细胞的损伤作用。结果：损伤组与对照组神经细胞损伤后LDH值比较差异有显著性(P＜0．05)证明损伤模型确实有效;本实验表明治疗组神经元LDH水平与损伤组比较有差异(P＜0．05),证明BDNF能够起神经元保护作用。结论：本实验表明BDNF对神经元起保护作用。     

几种药物、中间体合成新工艺

普卢利沙星关键中间体新工艺研究 普卢利沙星是最新一代氟喹诺酮类广谱抗菌药物,它对革兰氏阳性和阴性菌等多种细菌的抗菌力远远超过目前上市的其它氟喹诺酮类药物和抗生素药物,该药口服吸收好,耐受性好,反复给药在体内无蓄积,副作用很小,几乎没有其它氟喹诺酮药物常见的光毒性、肝脏毒性及中枢神经毒性,是第三代氟喹诺酮类药物中安全性极好的品种,临床应用前景广阔。     

喹诺酮类药物的不良反应

从1985年至今，在氟喹诺酮类药物的进展中，严重的药物不良反应受到关注，包括有光毒性的依诺沙星，培氟沙星，氟罗沙星；替马沙星与严重的溶血性尿毒症的并发症有关；洛美沙星引起光毒性并对中枢神经系统有影响，司帕沙星与光毒性和QT间期延长有关；托氟沙星引起严重的血小板减少症和肾炎；曲伐沙星有肝毒性，格帕沙星由于对心血管的影响而被撤出市场，克林沙星与光毒性和血糖过少有关。奎诺酮类药物的结构直接与其活性和不良反应相关，连接在喹诺酮母核上的特殊的取代基的关系已被阐明，日本在药物上市后5年的市场监督研究表明，氟喹诺酮相关性特殊的不良反应发生率，左氧氟沙星为1．3％，帕珠沙星为3．3％，托氟沙星为3．6％，加替沙星为4．5％，巴洛沙星为5．4％，胃肠反应是所有氟喹诺酮类药物中最常见的不良反应，在研究的喹诺酮类药物中，左氧氟沙星对中枢神经系统和皮肤的不良反应最低。     

环丙沙星注射液的药效与临床应用

环丙沙星是一种新型氟代喹诺酮衍生物,与其他喹诺酮类相比,有较强的抗菌活性和较广的抗菌谱。经体内抗菌作用与体外敏感实验证明,本品明显优于氨苄青霉素、头孢唑林、庆大霉素及苯唑青霉素。环丙沙星对肠杆菌科抗菌作用更强,对绿脓肝菌、革兰氏阳性球菌作用比其他氟喹诺酮类强,对流感杆菌、淋球菌有很强的活性。且与青霉素类、头孢菌素类及氨基糖苷类抗生素无交叉耐药作用。具有抗菌范围广,抗菌活力     

北京市部分医院门、急诊经验性选择抗生素调查分析

目的 :了解北京市部分医院门、急诊常见感染抗生素的选择。方法 :采用问卷的方法调查北京协和医院、北京友谊医院、北京天坛医院、北京大学附属第三医院、解放军第 30 1医院等 15家医院教授 (A组 )、主治医师 (B组 )、住院医师 (C组 )、进修医师(D组 )对 3种常见门、急诊感染 (急性膀胱炎、急性上呼吸道感染、急性细菌性肠炎 )的抗生素选择 ,并对结果作统计学分析。结果 :共收到北京协和医院问卷 16 1份 ,收到其他医院 32 3份。急性上呼吸道感染 ,青霉素类和加 β-内酰胺酶抑制剂的青霉素类几乎占所有抗生素的 5 0 %以上。A组 ,协和医院选择第 2代头孢菌素比例高 ,而其他医院选择加酶抑制剂青霉素类的比例较高 (P<0 0 5 ) ;B组 ,协和医院选择大环内酯类抗生素占第 1位 ,与其它医院有显著性差异 (P <0 0 5 ) ;选择氟喹诺酮类抗生素者均少。急性膀胱炎 ,氟喹诺酮抗生素是各组的首选 ,协和医院A组甚至达到了 10 0 % ,与其它医院 (6 1 1% )比较 ,有显著性差异 (P <0 0 5 )。急性细菌性肠炎 ,选择氟喹诺酮和氨基糖苷抗生素的比例在各组均达到 90 %以上。与急性膀胱炎相似 ,协和医院医师更偏向于氟喹诺酮 (氟喹酮类 氨基糖苷类 =2 1) ,而其他医院选择氟喹诺酮和氨基糖苷类抗生素的比例接近 1∶1。结论 :(1     

Phototoxicity studies of pazufloxacin mesilate,a novel parenteral quinolone antimicrobial agent--in vitro and in vivo studies

Phototoxicity of pazufloxacin mesilate (PZFX mesilate), a novel parenteral quinolone antimicrobial agent, were evaluated in vitro and in vivo studies. In vitro, phototoxicity for cultured cells of PZFX, which is active principle of PZFX mesilate, was studied, and stability for long-wavelength ultraviolet (UVA) was examined. In vivo, phototoxicity tests in guinea pigs and rats, and photoallergenicity tests in guinea pigs were conducted. In the phototoxicity test on cultured cells, CHL/IU cells were irradiated UVA of 300-3000 mJ/cm2 in the presence of PZFX, ofloxacin (OFLX), lomefloxacin (LFLX) or sparfloxacin (SPFX) at 10 micrograms/mL. Phototoxic potencies for cultured cells of the quinolones tested were SPFX > LFLX > OFLX > PZFX. In addition, changes in ultraviolet absorption spectrum and residual rate of PZFX, OFLX, LFLX and SPFX were examined after UVA irradiation of 300-3000 mJ/cm2 to each solution. PZFX was stable for UVA compared with OFLX and LFLX. In the phototoxicity test of guinea pigs, each quinolone was administered intraperitoneally daily for 7 days, and UVA of about 11 J/cm2 was irradiated at 30 minutes after the last administration. Dose levels of each quinolone were 65 and 130 mg/kg of PZFX mesilate (dose levels converted to PZFX: 50 and 100 mg/kg), 50 and 100 mg/kg of nalidixic acid (NA), 100 mg/kg of OFLX, enoxacin (ENX), ciprofloxacin (CPFX), LFLX and SPFX. Grade of skin reaction (erythema) at 24 hours after UVA irradiation decreased in the order: SPFX > CPFX > NA > ENX = OFLX > LFLX > PZFX mesilate. Thus, PZFX mesilate was found to have the weakest phototoxicity. In the maximum plasma concentration of quinolones from 0.5 to 2.5 hours after administration, corresponding to the time of UVA irradiation, the concentration of the group administered PZFX mesilate was about 4.1 times higher than that of CPFX group, and about 1.3 times higher than that of SPFX group. The area under the blood concentration-time curve (AUC0.5-2.5) of the group administered PZFX mesilate was the same as that of SPFX group, and about 3.2 times larger than that of CPFX group. These data showed that phototoxicity of PZFX mesilate was also weaker than that of CPFX or SPFX in consideration of AUC0.5-2.5. In the phototoxicity test of rats injected intravenously, no phototoxicity was observed at 130 mg/kg of PZFX mesilate. In the photoallergenicity test of guinea pigs, no photoallergenicity was observed by PZFX mesilate. As mentioned above, from in vitro studies PZFX was found to be stable for UVA irradiation compared with OFLX and LFLX, and phototoxicity for cultured cells of PZFX was weaker than that of SPFX, LFLX or OFLX. In addition, from in vivo studies phototoxicity of PZFX mesilate was found to be weaker than that of NA, OFLX, ENX, CPFX, LFLX or SPFX, and no photoallergenicity was observed. Therefore, photosensitive potency of PZFX mesilate might be less than that of other quinolones.     

Compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones

AIM: To compare two methods of measuring DNA damage induced by photogenotoxicity of fluoroquinolones(FQ). METHODS: Lomefloxacin (LFLX), sparfloxacin (SPFX), ciprofloxacin (CPFX), and levofloxacin (LELX)were tested by comet assay and photodynamic DNA strand breaking activity under the different conditions of UVA irradiation. RESULTS: In comet assay, photogenotoxicity was evident at SPFX 1mg/L, LFLX 5mg/L, and CPFX 5mg/L, and LELX 10mg/L. In photodynamic DNA srand-breaking activity, SPFX and LFLX induced the conver sion of the supercoiled form into the nicked relaxed form at 10-50μmol/L, while CPFX at 25μmol/L and LELX at 50μmol/L. CONCLUSION: There were good correlations between the two methods to detect DNA damage induced by phototoxicity of fluoroquinolones. Photodynamic DNA strand breaking activity was a good method to detect DNA damage induced by photogenotoxicity of fluoroquinolones as well as comet assay.     

Drug interactions between nonsteroidal anti-inflammatory drug and pazufloxacin mesilate,a new quinolone antibacterial agent for intravenous use: convulsions in mice after intravenous or intracerebroventricular administration

Convulsant activity of pazufloxacin mesilate (PZFX mesilate), a new quinolone antibacterial agent for intravenous use, in combination with nonsteroidal anti-inflammatory drug (NSAID) was investigated in mice after intravenous or intracerebroventricular administration. Following results were obtained. 1. In combination with 4-biphenylacetic acid (BPAA) at an oral dose of 100 mg/kg, PZFX mesilate did not induce any convulsions at intravenous doses up to 200 mg/kg. Reference quinolones induced convulsions at the following intravenous doses: Enoxacin (ENX), 3.13 mg/kg or more; norfloxacin (NFLX) and lomefloxacin (LFLX), 6.25 mg/kg or more; ciprofloxacin (CPFX), 50 mg/kg or more; sparfloxacin (SPFX) and temafloxacin (TMFX), 100 mg/kg or more; fleroxacin (FLRX), 200 mg/kg. 2. PZFX mesilate at an intravenous dose of 50 mg/kg did not induce convulsions in mice after oral administration of any of 14 kinds of NSAIDs. It induced convulsions at 200 mg/kg in combination with aspirin at an oral dose of 600 mg/kg, while it did not with the other 13 kinds of NSAIDs. 3. Convulsion-inducing dose of PZFX mesilate after intracerebroventricular administration was 100 mg/body, which was higher than those of reference quinolones (NFLX, CPFX, ENX, LFLX, TMFX, levofloxacin, ofloxacin, FLRX and SPFX) and beta-lactam antibiotics (penicillin G, cefazoline, imipenem/cilastatin and panipenem/betamipron). In addition, concurrent dosing of BPAA (1 microgram/body) did not reduce the convulsion-inducing dose of PZFX mesilate. These results suggest that PZFX mesilate has remarkably weak convulsant activity.     

司帕沙星和妥舒沙星的体内外抗菌作用研究

目的观察国产司帕沙星、妥舒沙星及其它四种氟喹诺酮类抗菌药对成都地区780株临床分离菌的体外抗菌活性，并比较司帕沙星、妥舒沙星和环丙沙星对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠的体内抗菌活性。方法用琼脂稀释法测定国产司帕沙星和妥舒沙星的MIC50和MIC90，并与其它四种氟喹诺酮类抗菌药进行了比较。本文还测定了抗菌药对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠治疗的ED50结果体外试验表明司帕沙星和妥舒沙星能有效抑制或杀灭革兰阳性、革兰阴性菌及厌氧菌，显示了广谱抗菌活性。司帕沙星和妥舒沙星对革兰阳性菌的抗菌活性是环丙沙星的2～8倍，氧氟沙星和氟罗沙星的4～16倍，是诺氟沙星的16～32倍。司帕沙星对MRSA的抗菌活性与妥舒沙星相似，但优于环丙沙星、氧氟沙星、氟罗沙星和诺氟沙星。司帕沙星对大多数革兰阴性菌的抗菌活性与环丙沙星和妥舒沙星相似，是氧氟沙星、氟罗沙星和诺氟沙星的2～8倍。两药对厌氧菌的抗菌活性也较环丙沙星强。口服或皮下注射司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。三种受试药对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于铜绿假单胞菌所致感染。结论司帕沙星和妥舒沙星对革兰阳性菌和厌氧菌的体外抗菌活性优于环丙沙星和其它药物，对大多数革兰阴性菌的抗菌活性与环丙沙星相似，但优于其它受试药。司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的体内保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。     

Apoptotic photoreceptor cell death induced by quinolone phototoxicity in mice

We examined retinal degeneration induced by phototoxicity of quinolone antibacterial agents. Albino Balb/c and pigmented DBA/2 mice fasted overnight were given a single oral administration of ciprofloxacin (CPFX), levofloxacin (LVFX), enoxacin (ENX), lomefloxacin (LFLX) or sparfloxacin (SPFX), followed by ultraviolet-A (UVA) irradiation at 1.5 mW/cm2 for 4 h (21.6 J/cm2). At 24 h after quinolone administration, the mice were sacrificed, and the eyes were then histologically examined. ENX or LFLX at 200 or 400 mg/kg or SPFX at 50 or 100 mg/kg plus UVA induced retinal degeneration in Balb/c mice, whereas no histological change was observed in the eyes of DBA/2 mice. CPFX and LVFX at 800 mg/kg plus UVA had no effect on the eyes in either Balb/c or DBA/2 mice. Agarose gel electrophoresis showed that chromosomal DNA extracted from the eyes of Balb/c mice was fragmented in the SPFX 100 mg/kg group, but not in the LVFX 800 mg/kg group. In the electron microscopic examination, swelling of mitochondria and disruption of the cytoplasm were observed in the photoreceptor inner segment (PIS) at 2 h, and disarrangement of lamellar disks in the outer segment (POS) and condensed chromatin in photoreceptor cell nuclei in the outer nuclear layer (ONL) were observed at 4 h after 100 mg/kg SPFX administration to Balb/c mice. These results suggest that quinolone plus UVA irradiation induces retinal degeneration in albino Balb/c mice, but not in DBA/2 mice, and this degeneration is associated with apoptotic photoreceptor cell death.     

Comparison of an in vitro cellular phototoxicity model against controlled clinical trials of fluoroquinolone skin phototoxicity.

Many therapeutic drugs induce phototoxic skin responses following exposure to solar or artificial ultraviolet radiation sources. Several in vitro model systems have been developed to predict drug phototoxicity but none have been conducted in parallel with controlled clinical phototoxicity studies on systemically administered pharmaceuticals. The in vitro phototoxicity of eight fluoroquinolone (FQ) antibiotics (ciprofloxacin, grepafloxacin, lomefloxacin, norfloxacin, ofloxacin, trovafloxacin, BAYy3118, moxifloxacin) was determined by exposing Chinese hamster fibroblasts to UVA radiation. Cell damage was quantified with standard MTT or neutral red assays and an in vitro phototoxic index calculated (PI(vit)=% cell viability with UVA alone /% cell viability with UVA+FQ) for each endpoint. Clinical photosensitizing ability of the eight systemically administered FQ was investigated using double-blind, placebo and positive controlled, clinical skin phototesting of normal subjects. Minimal erythema doses at 365+/-30nm were determined before and after 6-7 days of FQ ingestion and PI(clin) (minimal erythema dose without FQ/minimal erythema dose with FQ) calculated. Linear regression analysis of PI(vit) vs PI(clin) gave correlations of up to 0.893. Principal components analysis of PI(vit), daily dose, plasma levels and photophysical (absorption) properties of the eight FQ showed that phototoxic (arbitrarily defined as PI(clin)> or =2) and non-phototoxic (PI(clin)<2) FQ could be completely discriminated using these parameters, and that the in vitro models were able to rank the relative phototoxic potential of the eight FQ.     

Comparative study on salivary distribution of fluoroquinolones in rats

As a basic approach to identifying the distribution mechanism of quinolone antibiotics into saliva, salivary excretion of five fluoroquinolones, ciprofloxacin (CPFX), norfloxacin (NFLX), lomefloxacin (LFLX), ofloxacin (OFLX) and sparfloxacin (SPFX), was compared in rats. Blood, parotid and mandibular saliva were periodically collected from the anesthetized rats after bolus i.v. administration (10 mg/kg) of the quinolones. Quantification of the fluoroquinolones was performed by HPLC methods. The saliva-to-plasma unbound concentration (S/Pu) ratios of the fluoroquinolones in parotid saliva were larger than those of mandibular saliva. These five quinolones had considerably different S/Pu ratios from 0.014 to 1.497, while the S/Pu ratios theoretically calculated by the pH-partition theory were around 1.0 to 1.3, which showed no relationship to the corresponding measured ratios. Satisfactory linear correlations were observed in the plots of measured S/Pu ratios against 1-octanol-water partition coefficients of the fluoroquinolones in both types of saliva. These results indicate that fluoroquinolones possess different diffusibility in salivary distribution among the drugs and between parotid and mandibular glands. It was also clarified that the lipophilicity of the fluoroquinolones primarily determines the extent of salivary excretion.     

国产洛美沙星的体内抗菌作用研究

研究国产洛美沙星对３种致病菌感染的体内保护作用。小鼠灌胃洛美沙星对金黄色葡萄球菌感染的保护作用为诺氟沙星的３倍，环丙沙星的２倍；对大肠杆菌感染的保护作用是诺氟沙星的８倍，而略逊于环丙沙星；对绿脓杆菌的保护作用则是诺氟沙星的３～４倍，与环丙沙星相似或略差。小鼠静注洛美沙星亦表现明显的抗菌活性，并优于口服给药。结果显示，本品对３种细菌感染的保护作用明显优于诺氟沙星而具有良好的体内抗菌作用。     

Combined Use of In Vitro Phototoxic Assessments and Cassette Dosing Pharmacokinetic Study for Phototoxicity Characterization of Fluoroquinolones

The present study aimed to develop an effective screening strategy to predict in vivo phototoxicity of multiple compounds by combined use of in vitro phototoxicity assessments and cassette dosing pharmacokinetic (PK) studies. Photochemical properties of six fluoroquinolones (FQs) were evaluated by UV spectral and reactive oxygen species (ROS) assays, and phototoxic potentials of FQs were also assessed using 3T3 neutral red uptake phototoxicity test (3T3 NRU PT) and intercalator-based photogenotoxicity (IBP) assay. Cassette dosing pharmacokinetics on FQs was conducted for calculating PK parameters and dermal distribution. All the FQs exhibited potent UV/VIS absorption and ROS generation under light exposure, suggesting potent photosensitivity of FQs. In vitro phototoxic risks of some FQs were also elucidated by 3T3 NRU PT and IBP assay. Decision matrix for phototoxicity prediction was built upon these in vitro data, taken together with outcomes from cassette dosing PK studies. According to the decision matrix, most FQs were deduced to be phototoxic, although gatifloxacin was found to be less phototoxic. These findings were in agreement with clinical observations. Combined use of in vitro photobiochemical and cassette dosing PK data will be useful for predicting in vivo phototoxic potentials of drug candidates with high productivity and reliability.     

Possible involvement of P-glycoprotein in the biliary excretion of grepafloxacin

1. In the present study, we have examined the effects of the quinolones norfloxacin (NFLX), enoxacin (ENX), ofloxacin (OFLX), tosufloxacin (TFLX), lomefloxacin (LFLX), sparfloxacin (SPFX) and grepafloxacin (GPFX) on the efflux of doxorubicin from mouse leukaemia P388/ADR cells expressing P-glycoprotein. The relationship between their partition coefficients (hydrophobicity) and effluxing potencies was also elucidated. 2. Both TFLX and SPFX strongly increased the intracellular accumulation of doxorubicin (5 micromol/L) in P388/ADR cells, but had no effect on P388/S cells not expressing P-glycoprotein. The rank of order of the potency of the quinolones (TFLX > SPFX > GPFX > NFLX) was not related directly to their hydrophobicity. These results suggest that some quinolones can reverse anticancer drug resistance. 3. Because GPFX is more highly excreted into the bile than other known quinolones, the effects of doxorubicin (10 mg/kg) or the well-known inhibitors of P-glycoprotein, namely cyclosporine A (10 mg/kg) and erythromycin (100 mg/kg), on the biliary excretion of GPFX at steady state was studied in rats. 4. Doxorubicin, cyclosporine A and erythromycin significantly decreased the biliary clearance of GPFX. Cyclosporine A and erythromycin had a much stronger inhibitory effect on the biliary excretion of GPFX than doxorubicin. These results suggest the possibility that GPFX is, at least in part, excreted into the bile by a P-glycoprotein-mediated transport mechanism.