血浆同型半胱氨酸与冠脉狭窄程度及病变支数的相关性研究

目的探讨血浆同型半胱氨酸( Hcy)与冠脉狭窄程度及病变支数的相关性。方法回顾性纳入 2018年 1月至 2018年 9月重庆医科大学附属永川医院已行冠状动脉造影且结果为阳性的冠脉狭窄病人 103例,根据血浆 Hcy水平将其分为高同型半胱氨酸组( HHcy,Hcy≥10 μmol/L)71例和正常同型半胱氨酸组( NHcy,Hcy＜10 μmol/L)32例,所有纳入病人均完善血浆同型半胱氨酸、尿酸以及血脂检测,采用冠脉 Gensini评分评估冠脉狭窄程度。结果 HHcy组的平均收缩压［(140±20)mmHg比(136±19)mmHg,P＝0.381)］、平均舒张压［(84±13)mmHg比( 83±13)mmHg,P＝0.752)］、尿酸［(413.0±130.6)μmol/L比( 346.0± 97.8)μmol/L,P＝0.012)］、总胆固醇［(4.4±1.0)mmol/L比( 4.1±1.1)mmol/L,P＝0.216)］、总三酰甘油［(1.6±0.9)mmol/L比( 1.5± 0.7)mmol/L,P＝0.741)］及低密度脂蛋白胆固醇水平［(2.5±0.8)mmol/L比( 2.3±0.9)mmol/L,P＝0.129)］均高于 NHcy组,冠脉 Gensini评分与 Hcy及低密度脂蛋白胆固醇水平呈正相关( r＝0.2,0.2;p＝0.012,0.012)Hcy水平能显著影响冠脉 Gensini评分,且 Hcy水平越高,冠脉 Gensini评分越高(相关系数＝ 0.804,P＝0.015); NHcy组冠脉病变占 50%,双支病变占 40.6%,三支病变占 9.4%,HHcy组中单支病变占 25.4%,双支病变占 33.8%,三支病变占 40.8%(χ2＝11.38,P＝0.03)。结论血浆 Hcy水平及低密度脂蛋白胆固醇与冠脉狭窄程度呈正相关,但相关性较弱,高水平的同型半胱氨酸是冠脉严重病变的独立危险因素,且会增加冠脉三支病变的发生率。     

血浆同型半胱氨酸水平与冠状动脉病变关系的研究

目的研究冠心病患者血浆同型半胱氨酸(HCY)水平与冠心病的关系.方法选择87例经冠脉造影证实的冠心病患者(心肌梗死或心绞痛)和52例冠脉造影结果未见异常的正常人群做对照,采用高压液相色谱法测定HCY血浆水平.结果(1)对照组血浆HCY水平(10.29±3.74)μmol/L,较冠心病组(15.02±5.38)μmd/L为低(P<0.01).(2)冠心病组中冠状动脉单支病变组血浆HCY水平(¨.78±3.91)μmd/L,较≥2支病变组(16.72±5.29)μmol/L为低(P<0.01).(3)冠心病组中有其它危险因素者与无其它危险因素者比较血浆HCY水平无显著差异(P>0.05).结论高同型半胱氨酸血症可能是冠心病的独立危险因素,其水平在冠脉单支病变组较≥2支病变组为低.     

罗格列酮对糖尿病患者血浆同型半胱氨酸水平的影响

目的探讨罗格列酮对2型糖尿病患者血浆总同型半胱氨酸水平的影响。方法采用高效液相色谱法测定20名健康对照者、46例新诊断2型糖尿病患者血浆总同型半胱氨酸水平。对比口服罗格列酮治疗2个月前后血总同型半胱氨酸改变。结果2型糖尿病患者血浆总同型半胱氨酸水平(15±3)μmol/L高于对照组[(8±3)μmol/L,P<0.05],并且总同型半胱氨酸水平与年龄、体重指数(BMI)、空腹血糖(FBG)和空腹胰岛素水平(FINS)呈明显正相关(P<0.05),与尤岛素敏感指数呈负相关。罗格列酮治疗2个月后,血浆总同型半胱氨酸水平(12±5)μmol/L比治疗前降低(P<0.05)。结论2型糖尿病患者血浆总同型半胱氨酸水平增高,罗格列酮治疗后可降低其水平。     

血液灌流对维持性血液透析患者同型半胱氨酸精氨酸加压素及内皮素的影响

目的检测维持性血液透析患者血清同型半胱氨酸(Hcy)、精氨酸加压素(AVP)及内皮素的水平,并观察血液灌流对三者的影响。方法选择维持性血液透析患者60例,随机分为血液灌流串联血液透析组(HP+HD组)和单纯血液透析组(HD组),每组30例,分别于治疗前、后采静脉血;健康人25名为对照组;成批检测血中Hcy、AVP和内皮素的水平。采用单因素方差分析进行数据分析。结果①HP+HD组治疗前血Hcy、AVP和内皮素水平分别为:(13.4±1.0)μmol/L,(354±49)ng/L,(142±16)ng/L;HD组分别为:(14.0±1.3)μmol/L,(348±43)ng/L,(142±14)ng/L;均明显高于对照组[分别为:(7.2±0.9)μmol/L,(256±41)ng/L,(115±10)ng/L],差异均有统计学意义(P<0.05);HP+HD组和HD组治疗前各因子水平差异无统计学意义。②HP+HD组在治疗后血Hcy、AVP和内皮素水平分别为:(8.7±0.9)μmol/L,(265±39)ng/L,(119±12)ng/L,较治疗前显著下降,差异均有统计学意义(P<0.05);而HD组在治疗前后各因子水平差异无统计学意义。结论维持性血液透析患者血清Hcy、AVP和内皮素水平较健康人明显升高,血液灌流串联血液透析可以有效降低其在体内的水平。     

同型半胱氨酸与急性脑梗死关系的研究

目的探讨同型半胱氨酸与急性脑梗死的关系。方法急性脑梗死患者60例,随机选取门诊进行健康体检者60例作为对照,分别检测两组患者的同型半胱氨酸水平和血总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白,比较两组患者所检测指标的不同。结果病例组同型半胱氨酸水平(17.85±7.30)μmol/L,显著高于对照组水平(10.22±3.71)μmol/L(P<0.01);病例组血总胆固醇、甘油三酯、高密度脂蛋白、低密度脂蛋白之间无显著性相关(均P>0.05)。结论高同型半胱氨酸是脑梗死的独立危险因素,补充维生素、叶酸,降低高同型半胱氨酸水平,可能是防治脑血管病的一个有效途径。     

测定急性冠状动脉综合征患者血浆同型半胱氨酸的意义

目的探讨冠心病(CHD)尤其是急性冠状动脉综合征(ACS)患者血浆同型半胱氨酸(Hcy)及影响因素叶酸、维生素B12等水平变化与冠状动脉病变严重性之间的关系。方法采用荧光偏振免疫分析法、离子捕获免疫分析法及非均相微粒子酶免疫分析法等测定302例CHD患者,包括ACS组202例(急性心肌梗死组132例和不稳定型心绞痛组70例),稳定型心绞痛(SAP)组100例和正常对照组120例的血浆Hcy、叶酸及维生素B12等水平。对冠心病患者的冠状动脉损害行Gensini评分,并比较各组间的差异。结果①ACS组、SAP组Hcy浓度显著高于对照组[(19±12)μmol/L vs (10±6)μmol/L(P<0.01)、(15±5)μmol/L vs (10±6)μmol/L(P<0.01)],而叶酸,维生素B12浓度显著低于对照组[(3.2±0.7)μg/L vs (7.1±1.8)μg/L(P<0.01),(5.3±0.6)μg/L vs (7.1±1.8)μg/L(P<0.01);(184±32)ng/L vs (283±56)ng/L(P<0.01),(228±45)ng/L vs (283±56)ng/L(P<0.01)。并且ACS组和SAP组的血浆同型半胱氨酸和血清叶酸、维生素B12浓度差异也有统计学意义。②血浆Hcy浓度与血浆叶酸、维生素B12浓度呈线性负相关。③随着冠状动脉病变Gensini评分的增加,Hcy浓度明显升高。结论冠心病尤其是ACS患者血浆Hcy显著升高,其升高严重程度与CHD的发生、病情严重性和冠状动脉病变程度有密切关系,检测CHD患者血浆Hcy水平可以预测冠状动脉病变程度,对于高Hcy者应用叶酸,维生素B12治疗,对于延缓CHD尤其是ACS病变发展可能有十分重要的临床意义。     

血清HCY在脑梗死合并糖尿病患者中表达的意义

目的探讨血清同型半胱氨酸在脑梗死合并糖尿病患者中表达的意义。方法选取笔者所在医院2010~2011年间收治的脑梗死患者78例作为实验组,选取35例健康志愿者作为对照组,分别对两组血清同型半胱氨酸水平进行测定和统计学分析。结果实验组中合并糖尿病患者血清同型半胱氨酸水平为(17.35±7.62)μmol/L,显著高于无糖尿病者(14.35±6.35)μmol/L,差异有统计学意义(P<0.05)。实验组血清同型半胱氨酸水平高于对照组(10.36±4.61)μmol/L,差异有统计学差异(P<0.05)。结论血清同型半胱氨酸在脑梗塞及合并糖尿病患者中均显著升高,其可能与脑梗死及糖尿病的发生有关。     

叶酸和复合维生素B对血液透析患者血浆同型半胱氨酸水平的影响

目的观察叶酸和复合维生素B联合用药对维持性血液透析(HD)患者血浆同型半胱氨酸(Hcy)水平的影响。方法对48例稳定HD超过三个月成年患者的血浆Hcy水平以及对叶酸和复合维生素B治疗的反应进行了前瞻性随机对照研究。所有患者口服叶酸5mg/d,3个月后随机分成联合治疗组(叶酸+复合维生素B)和对照组(叶酸+安慰剂),每次血液透析后联合治疗组静脉注射复合维生素B1支,对照组静脉注射等量的生理盐水,疗程3个月。观察治疗前后患者血浆Hcy水平的变化。结果HD患者的血浆Hcy水平明显增高[(33.25±4.54)μmol/L]并伴随维生素B12的不足[(320.7±25.2)pmol/L]。口服叶酸5mg/d3个月后,血浆Hcy降至(23.83±4.51)μmol/L(P<0.01);叶酸和复合维生素B联合治疗6个月,患者的血浆维生素B12水平明显高于对照组[(631.4±60.9)pmol/L与(317.6±49.2)pmol/L,P<0.001],血浆Hcy水平下降程度高于对照组[(18.69±3.91)μmol/L与(23.95±4.32)μmol/L,P<0.05]。结论HD患者普遍存在高Hcy血症,并伴随维生素B12水平的不足。补充叶酸能有效降低HD患者血浆Hcy水平;联合使用复合维生素B能更进一步地改善高Hcy血症。     

血同型半胱氨酸与2型糖尿病肾病发病的关系

目的探讨同型半胱氨酸(HCY)与2型糖尿病肾病患者的关系。方法根据糖尿病患者24h尿白蛋白排泄率(UAE)分为三组:无肾病组、早期肾病组和临床蛋白尿组。同时用荧光偏振分析法测定患者总同型半胱氨酸浓度,并常规生化仪监测空腹血糖。结果合并早期肾病组平均HCY与无肾病组比较有明显差异[(26·16±12·31)μmol/L与(8·79±3·51)μmol/L,P<0·01]。临床蛋白尿组HCY虽高于早期肾病,但无统计学意义[(30·15±10·35)μmol/L与(26·16±12·31)μmol/L,P>0·05]。随着蛋白尿的增多而血清同型半胱氨酸也相应增加。结论高HCY可能与糖尿病肾病有关,是患者的独立危险因素。     

血浆同型半胱氨酸与冠状动脉病变的关系

目的 :探讨血浆同型半胱氨酸 (Hcy)与冠状动脉病变及累及病变支数的关系。方法 :对121名行冠状动脉造影术的患者进行血浆Hcy、叶酸、维生素B12 的检测。其中冠心病组83人 ,非冠心病组38人 ,冠心病组又根据病变支数分为单支病变组 (25例 )、双支病变组 (35例 )、三支病变组 (23例 )。结果 :冠心病组的血浆Hcy水平为 (16 06±6 98) μmol/L ,明显高于非冠心病组(11 11±4 27) μmol/L ,P<0 001。冠心病组的单支、双支、三支病变组其血浆Hcy 均显著高于非冠心病组 ,但三者之间差异无显著性。结论 :血浆Hcy 增高是冠状动脉病变的独立危险因素 ,血浆Hcy 水平可能与累及冠状动脉支数无关。     

Susceptibility to erythromycin of anaerobes of the genera Bacteroides, Fusobacterium, Sphaerophorus, Veillonella, Clostridium, Corynebacterium, Peptococcus, Peptostreptococcus

The minimal inhibitory concentrations (MIC) of erythromycin were determined by broth dilution tests for 313 anaerobic strains, most of which were clinical isolates. All the gram-positive anaerobes tested (84 Peptococcaceae, including 21 Peptostreptococcus anaerobius and 15 Peptococcus variabilis; 65 Corynebacterium acnes and 29 Clostridium strains, including 13 C. perfringens) were sensitive (MIC values 0.012 through 3.12 microgram erythromycin/ml); so were 111 cultures of gram-negative anaerobes (52 Bacteroides fragilis, 12 B. thetaiotaomicron, 7 B. vulgatus, 13 B. oralis, 4 B. melaninogenicus, 10 Sphaerophorus necrophorus, 2 Veillonella sp., 11 members of other species). Erythromycin at concentrations of 6.25 through 200.0 microgram/ml was active against 24 strains (1 B. fragilis, 4 Fusobacterium fusiforme, 9 Sph. freundi, 10 Sph. varius). The present results are compared to the limited number of reports existing with regard to the susceptibility of anaerobes to erythromycin.     

Safety assessment of poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate as used in cosmetics

Poloxamers are polyoxyethlyene, polyoxypropylene block polymers. The impurities of commercial grade Poloxamer 188, as an example, include low-molecular-weight substances (aldehydes and both formic and acetic acids), as well as 1,4-dioxane and residual ethylene oxide and propylene oxide. Most Poloxamers function in cosmetics as surfactants, emulsifying agents, cleansing agents, and/or solubilizing agents, and are used in 141 cosmetic products at concentrations from 0.005% to 20%. Poloxamers injected intravenously in animals are rapidly excreted in the urine, with some accumulation in lung, liver, brain, and kidney tissue. In humans, the plasma concentration of Poloxamer 188 (given intravenously) reached a maximum at 1 h, then reached a steady state. Poloxamers generally were ineffective in wound healing, but were effective in reducing postsurgical adhesions in several test systems. Poloxamers can cause hypercholesterolemia and hypertriglyceridemia in animals, but overall, they are relatively nontoxic to animals, with LD(50) values reported from 5 to 34.6 g/kg. Short-term intravenous doses up to 4 g/kg of Poloxamer 108 produced no change in body weights, but did result in diffuse hepatocellular vacuolization, renal tubular dilation in kidneys, and dose-dependent vacuolization of epithelial cells in the proximal convoluted tubules. A short-term inhalation toxicity study of Poloxamer 101 at 97 mg/m(3) identified slight alveolitis after 2 weeks of exposure, which subsided in the 2-week postexposure observation period. A short-term dermal toxicity study of Poloxamer 184 in rabbits at doses up to 1000 mg/kg produced slight erythema and slight intradermal inflammatory response on histological examination, but no dose-dependent body weight, hematology, blood chemistry, or organ weight changes. A 6-month feeding study in rats and dogs of Poloxamer 188 at exposures up to 5% in the diet produced no adverse effects. Likewise, Poloxamer 331 (tested up to 0.5 g/kg day(-1)), Poloxamer 235 (tested up to 1.0 g/kg day(-1)), and Poloxamer 338 (at 0.2 or 1.0 g/kg day(-1)) produced no adverse effects in dogs. Poloxamer 338 (at 5.0 g/kg day(-1)) produced slight transient diarrhea in dogs. Poloxamer 188 at levels up to 7.5% in diet given to rats in a 2-year feeding study produced diarrhea at 5% and 7.5% levels, a small decrease in growth at the 7.5% level, but no change in survival. Doses up to 0.5 mg/kg day(-1) for 2 years using rats produced yellow discoloration of the serum, high serum alkaline phosphatase activity, and elevated serum glutamicpyruvic transaminase and glutamic-oxalacetic transaminase activities. Poloxamers are minimal ocular irritants, but are not dermal irritants or sensitizers in animals. Data on reproductive and developmental toxicity of Poloxamers were not found. An Ames test did not identify any mutagenic activity of Poloxamer 407, with or without metabolic activation. Several studies have suggested anticarcinogenic effects of Poloxamers. Poloxamers appear to increase the sensitivity to anticancer drugs of multidrug-resistant cancer cells. In clinical testing, Poloxamer 188 increased the hydration of feces when used in combination with a bulk laxative treatment. Compared to controls, one study of angioplasty patients receiving Poloxamer 188 found a reduced myocardial infarct size and a reduced incidence of reinfarction, with no evidence of toxicity, but two other studies found no effect. Poloxamer 188 given to patients suffering from sickle cell disease had decreased pain and decreased hospitilization, compared to controls. Clinical tests of dermal irritation and sensitization were uniformly negative. The Cosmetic Ingredient Review (CIR) Expert Panel stressed that the cosmetic industry should continue to use the necessary purification procedures to keep the levels below established limits for ethylene oxide, propylene oxide, and 1,4-dioxane. The Panel did note the absence of reproductive and developmental toxicity data, but, based on molecular weight and solubility, there should be little skin penetration and any penetration of the skin should be slow. Also, the available data demonstrate that Poloxamers that are introduced into the body via routes other than dermal exposure have a rapid clearance from the body, suggesting that there would be no risk of reproductive and/or developmental toxicity. Overall, the available data do not suggest any concern about carcinogenesis. Although there are gaps in knowledge about product use, the overall information available on the types of products in which these ingredients are used, and at what concentration, indicates a pattern of use. Based on these safety test data and the information that the manufacturing process can be controlled to limit unwanted impurities, the Panel concluded that these Poloxamers are safe as used.     

HPLC法测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱

目的 采用高效液相色谱（HPLC）法同时测定抗妇炎胶囊中木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱10种活性成分。方法 采用InerSustain AQ-C₁₈色谱柱（250 mm×4.6 mm,5 μm）,流动相A：乙腈–无水乙醇（80∶20）,流动相B：0.1%磷酸溶液,梯度洗脱,检测波长220 nm,体积流量1.0 mL/min,柱温30℃,进样量10 μL。结果 木兰花碱、黄柏碱、药根碱、巴马汀、小檗碱、槐果碱、苦参碱、氧化槐果碱、槐定碱和氧化苦参碱分别在2.69～134.50、1.95～97.50、0.63～31.50、0.86～43.00、11.95～597.50、0.59～29.50、6.08～304.00、4.85～242.50、1.66～83.00、19.79～989.50 μg/mL线性关系良好（r≥0.999 3）;平均回收率分别为99.11%、98.23%、96.95%、97.78%、100.02%、97.21%、99.66%、99.52%、98.81%、100.08%,RSD值分别为1.04%、1.23%、1.37%、1.65%、0.70%、1.28%、0.65%、0.81%、1.11%、0.63%。结论 建立的HPLC法可用于抗妇炎胶囊中10种活性成分的测定,作为抗妇炎胶囊质量控制方法。     

Strength of drug habits: For heroin,morphine, methadone,alcohol, barbiturates,pentobarbital, benzedrine,cocaine, and marijuana

The drug habits for 78 confirmed opiate addicts were studied on eight scales from the Process Association Test of Addiction (PATA) for many drug names. Through cluster analysis eight stages of addiction were defined: “to be clean”, “to learn about drugs”, “to hustle”, “to chip” (also “to be high”), to be psychologically dependent or “to need a shot”, “to be hooked”, “to kick a habit” and “to be in treatment”. Associations stimulated by the words heroin and morphine were very similar over the eight stages of addiction in opiate addicts. The subjects were especially inclined to associate morphine and heroin with the most severe level of addiction, “to be hooked”. Associations to both methadone and cocaine were elevated at the “hooked” stage, but in other respects associations to these drugs were opposite. Thus, associations to cocaine were focused on the stage of psychological dependence and the lower intermediate stage of addiction, “to chip” and “to be high”, whereas associations to methadone suggested a turning away from addiction as indicated by avoidance associations (“to come down” and “to kick a habit”) as well as associations to “treatment” and “to be clean”. Marijuana, Benzedrine, “goofball” (barbiturates) and alcohol habits were prominent at an intermediate stage of addiction (“to chip” and “to be high”). Avoidance associations were common for Benzedrine and “goofballs” (also pentobarbital) but not for marijuana or alcohol. “Hustling” associations were frequent for marijuana but not for alcohol.     

Simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone

A gas-liquid chromatographic method for the simultaneous measurement of bupivacaine, etidocaine, lidocaine, meperidine, mepivacaine, and methadone in serum is described. The drugs and the internal standard, prilocaine, are extracted from 1 ml of serum. The procedure involves a two-step extraction and injection of the extract into a gas chromatograph equipped with a 10-ft OV-11 glass column and a nitrogen-phosphorus detector. The temperature gradient program results in a run time of 16 min and retention times for meperidine, prilocaine (internal standard), lidocaine, etidocaine, mepivacaine, methadone, and bupivacaine of 3.8, 5.4, 6.0, 8.7, 11.0, 11.7, and 14.8 min, respectively. Standard curves for all drugs were linear over the 80 to 2,000-ng/ml range and recovery of all components averaged 97 +/- 2% with the lowest detection limit of 10 ng/ml for all drugs except meperidine and methadone, which were 20 ng/ml. The within-day coefficients of variation ranged from 12 to 8% at 500 ng/ml. The day-to-day coefficients of variation of the slope and intercept values ranged from 2 to 0% and 130 to 3%, respectively. Response factors of the nitrogen-specific collector varied with the drug analyzed and resulted in peak area variation at constant offset and attenuation of 30%. This method is intended and adequate for therapeutic monitoring of chronically treated pain patients who are being given various combinations of local anesthetic and/or narcotic agents.     

New antiretroviral drugs: a review of the efficacy,safety, pharmacokinetics,and resistance profile of tipranavir,darunavir, etravirine,rilpivirine, maraviroc,and raltegravir

Background: The introduction and approval of new antiretroviral agents in the US and Canada bring new opportunities and new challenges. Arguably, for the first time ever, clinicians have the drugs necessary to achieve the goal of suppressing HIV RNA to levels less than 50 copies/mL in even the most treatment-experienced patients and in those with extensive drug-limiting resistance mutations. However, the use of these new agents is complicated by many drug–drug interactions and – to some extent – pre-existing mutations. To derive maximum durability from the use of these newer drugs, a thorough understanding of their indications and limitations is critical. Objective: To thoroughly review the six most recently approved or soon-to-be-approved antiretroviral drugs in the US and Canada: tipranavir, darunavir, etravirine, rilpivirine, maraviroc, and raltegravir. Methods: Discussion of the indications for, and pharmacokinetics, resistance profile, activity, toxicity, and clinical trials results of, the six new agents. Results/conclusions: These six new agents have resulted in marked progress towards the goal of being able to provide HIV-infected individuals with the drugs necessary to achieve decades of durable suppression of HIV without substantial toxicity.     

Disposition of fluvastatin, an inhibitor of HMG-COA reductase, in mouse, rat, dog, and monkey

The physiological disposition of fluvastatin, a potent inhibitor of hydroxymethylglutaryl-CoA reductase and thus cholesterol synthesis, has been studied in the mouse, rat, dog, and monkey using 14C- or 3H-labeled drug. Oral doses of fluvastatin were absorbed at a moderate to rapid rate. The extent of absorption was dose-independent and was essentially complete in all four species studied. However, the drug was subject to extensive presystemic hepatic extraction followed by direct excretion via the bile, thus minimizing the systemic burden and yielding high liver/peripheral tissue concentration gradients for fluvastatin and its metabolites. Only at high doses far exceeding the intended human daily dose of ca 0.6 mg kg-1 did fluvastatin bioavailability approach unity, apparently due to saturation of the first-pass effect. Dose-normalized blood levels of fluvastatin and total radioactivity were higher in the dog than in the other species, suggesting a smaller distribution volume in the former. Fluvastatin was partially metabolized before excretion, the extent of metabolism being smallest in the dog and greatest in the mouse. The half-life of intact fluvastatin ranged from 1-2h in the monkey to 4-7h in the dog. Regardless of the dose or dose route, the administered radioactivity was recovered predominantly in feces, with the renal route accounting for less than 8 per cent of the dose. No tissue retention of radioactivity was observed, and material balance was essentially achieved within 96h after dosing.