工艺注射用血塞通(冻干)Beagle犬急性毒性试验

目的采用Beagle犬一次静脉注射近似致死量测定法,观察单次静脉注射给予新、老工艺注射用血塞通(冻干)所产生的急性毒性反应及其性质和程度,为工艺改进提供试验依据。方法8只Beagle犬按性别和体重随机分为2组,即新、老工艺注射用血塞通(冻干)组,以2ml/kg体重的容积静脉注射给药,以100mg/kg为起始剂量,按50%剂量递增,观察给药后动物的急性毒性反应和死亡情况,并对犬的血清生化、血液学、血清电解质、尿、粪常规、体重增长、心电进行检测,寻找主要的毒性靶器官、无毒反应剂量及药物的安全范围。结果2种工艺100mg/kg剂量动物一般行为未见明显异常;150、225mg/kg剂量动物出现活动减少、肌肉抽搐震颤、瘙痒、呕吐、呼吸急促等症状,一般在3h内均能完全恢复;337mg/kg剂量动物给药后30min体温下降明显,萎靡、瘫痪,且全身皮肤增厚,头面部、耳朵、口腔周围粘膜潮红水肿,出现明显类变态反应,瘫痪一般在0.5~1h内能够恢复,局部粘膜潮红水肿在1~3h消失,精神萎靡在8h内恢复;给药后连续观察14d,各剂量动物血液、生化检测指标波动与给药无明显相关性;新、老工艺337mg/kg剂量动物摄食量减少,约第9天恢复正常摄食,体重增长缓慢,但无一死亡。结论在本实验条件下,Beagle犬单次静脉注射2种工艺注射用血塞通,毒性反应呈现剂量-反应关系,100mg/kg体重为无毒性反应剂量,近似致死量大于337mg/kg体重,为临床拟用剂量的101倍,可能涉及的毒性靶器官为中枢神经系统、自主神经系统;2种工艺注射用血塞通同等剂量在毒性反应上无明显差异,试验结果为工艺改进提供了试验依据。     

唑来膦酸急性毒性试验研究

按新药审批“急性毒性试验”的要求与方法 ,用昆明小鼠以灌胃、静脉注射两种给药途径进行了唑来膦酸急性毒性试验。结果显示 ,昆明小鼠口服给药受试物 LD50 为 713 .5 ( 667.8～ 763 .2 ) mg/kg;静脉给药 LD50 为 13 .8± 0 .8( 12 .6～ 14 .3 ) mg/kg。     

一类创新药苯胺洛芬注射液急性毒性研究

目的研究一类创新药苯胺洛芬的急性毒性,并与日本同类上市产品联苯乙酸乙酯注射液的急性毒性实验结果进行比较,为新药研发提供依据。方法选用NIH小鼠和Beagle犬为研究对象,采用最大耐受量法和近似致死量法考察一类创新药苯胺洛芬的急性毒性情况。结果苯胺洛芬NIH小鼠静脉注射给药最大耐受量为900 mg/kg,Beagle犬静脉滴注给药的近似致死剂量范围为405～608mg/kg(均以联苯乙酸计);联苯乙酸乙酯小鼠LD50分别为雄性337 mg/kg(294.5～347.4),雌性433 mg/kg(392.3～462.9);Beagle犬静脉滴注近似致死量为250～500 mg/kg(均以联苯乙酸计)。结论与联苯乙酸乙酯注射液相比,一类创新药苯胺洛芬注射液的安全性较好,安全范围较大,具有较好的应用前景。     

京尼平苷和西红花酸保肝利胆作用的比较

目的 :比较栀子果实中的 2个主要有效成分京尼平苷和西红花酸的保肝利胆作用。方法 :采用十二指肠给药 ,观察京尼平苷和西红花酸对大鼠胆汁流量的影响。采用小鼠CCl4,对乙酰氨基酚急性肝损伤模型 ,比较 2种药物对血清丙氨酸转氨酶 (ALT) ,天冬氨酸转氨酶 (AST)及肝组织中丙二酰二醛 (MDA) ,还原型谷胱甘肽(GSH) ,谷胱甘肽过氧化物酶 (GSH Px)的影响。结果 :京尼平苷 5 0和 10 0mg·kg-1剂量于给药后 0 .5h均显著增加大鼠胆汁分泌 ,而西红花酸同样 2个剂量于给药后 1h对大鼠胆汁分泌却有抑制作用。京尼平苷和西红花酸均可对抗CCl4和对乙酰氨基酚肝损伤引起的MDA升高 ,GSH含量下降和GSH Px活力降低。肝组织的病理变化也有明显减轻 ,但京尼平苷的作用明显强于西红花酸。结论 :栀子利胆保肝的有效成分主要为京尼平苷。     

Beagle犬经口给予六神丸急性毒性研究

目的六神丸全方单次给药毒性的再评价;六神丸配方对蟾酥组分的配伍毒性关系研究。方法分为六神丸全方组、六神丸去蟾酥组和蟾酥组。给Beagle犬经口灌胃给予药物,间隔2d提高剂量给药一次。结果在1.8~48.6mg/kg剂量范围内,六神丸去蟾酥组动物均未见明显异常;在5.4mg/kg以上剂量蟾酥配方组动物出现呕吐、稀便、活动减少等症状。在>1.8mg/kg剂量时,六神丸全方组动物出现呕吐、活动减少等症状,一只雌性动物出现进食量减少和体重下降的情况,并且在48.6mg/kg剂量时,一只雄性动物死亡。心电图:六神丸全方组和蟾酥配方组出现剂量依赖性心率减慢、S-T振幅降低和T波倒置等,但在16.2和48.6mg/kg剂量时,去蟾酥配方的Q波振幅增加。血液学:在毒性剂量(16.2和48.6mg/kg)时,出现红细胞数升高、血红蛋白浓度升高、红细胞比容升高、血小板数升高、淋巴细胞比例下降。血清生化学:在毒性剂量(16.2和48.6mg/kg)时,血清丙氨酸氨基转换酶、白蛋白及胆固醇水平均升高。结论六神丸配方对蟾酥组分未见明显减毒影响;Beagle犬灌胃给予六神丸的最大耐受剂量为1.8mg/kg,最小致死剂量为48.6mg/kg。     

班布特罗的急性毒性研究

对班布特罗盐酸盐的急性毒性进行了研究。结果表明 ,班布特罗盐酸盐对雄性小鼠尾静脉注射给药的 LD50 =96.3 7mg/ kg,对雌性小鼠尾静脉注射给药的 LD50 =83 .65 mg/ kg。班布特罗盐酸盐对雌性小鼠灌胃给药的 LD50 =70 5 .0 2 mg/ kg     

香丹葡萄糖注射液对犬长期静脉给药心电图及呼吸频率测试的实验研究

目的研究香丹葡萄糖注射液对犬静脉给药13周所致标Ⅱ导联心电图和呼吸频率的影响。方法将犬随机分为3组对照组、低剂量组、高剂量组,分别静脉注射5%葡萄糖注射液、生药1.6g/kg、8.0g/kg。试验期间于给药前、给药中期、给药结束及恢复期结束对每只存活动物测试心电图和呼吸频率。然后将低剂量组和高剂量组的结果分别与对照组比较,进行统计学分析。结果未发现有毒理学意义的统计学变化。结论连续对犬静脉注射香丹葡萄糖注射液13周,未引起犬标Ⅱ导联心电图和呼吸频率的改变。     

氚标记小牛胸腺DNA在大鼠和犬体内的药动学研究

目的:研究氚标记小牛胸腺DNA(3H-小牛胸腺DNA)在大鼠和Beagle犬体内的药动学特征。方法:采用氚水交换法制备3H-小牛胸腺DNA。取大鼠尾静脉注射高、中、低剂量(15、5、1.67 mg/kg,n=5)的3H-小牛胸腺DNA,中、高剂量组大鼠连续给药7d(第1、7天给予3H-小牛胸腺DNA,其余时间给予未标记小牛胸腺DNA),低剂量大鼠仅单次给药;另取犬前肢静脉注射高、中、低剂量(1.5、0.5、0.167 mg/kg,n=3)的3H-小牛胸腺DNA,中剂量犬连续给药7 d,低、高剂量犬仅单次给药。分别于第1、7天给药后0.033、0.25、1、2、4、6、8、12、24 h取血,分离血浆后加入闪烁液并使用液闪计数仪分析,以WinNonlin软件计算药动学参数。结果:高、中、低剂量3H-小牛胸腺DNA在大鼠体内的药动学参数分别为:单次给药的AUC0-24 h为(11 742±2 245)、(3 571±851)、(727±202)ng-Eq·h/g,t1/2为(21.4±5.08)、(13±6.0)、(6.8±1.76)h;重复给药高、中剂量的AUC0-24 h为(5 706±1 009)、(7 601±1 861)ng-Eq·h/g,t1/2为(16.0±10.13)、(9±2.7)h。高、中、低剂量3H-小牛胸腺DNA在犬体内的药动学参数分别为:单次给药的AUC0-24 h为(4 444±999)、(2 719±139)、(501±101)ng-Eq·h/g,t1/2为(17.6±7.57)、(14.0±1.76)、(16.4±2.39)h;重复给药中剂量的AUC0-24 h为(3 073±200)ng-Eq·h/g,t1/2为(20.6±6.62)h。结论:3H-小牛胸腺DNA在大鼠与Beagle犬体内单次给药和重复给药均可被快速消除。     

KNT009安全性药理学研究

目的:观察KNT009对小鼠神经系统、犬心血管系统及呼吸系统的影响。方法:实验均分高、中、低剂量组及空白对照和阳性对照共5个组,小鼠实验给药组分别单次慢速静脉注射(iv)KNT009 160、80和40 mg/kg,加替沙星80 mg/kg,观察动物的自发活动和爬杆能力;犬实验给药组分别单次慢速iv KNT009 40、20 和10 mg/kg,加替沙星20 mg/kg,观察药物对犬血压、ECG、呼吸频率及节律的影响。结果:单次慢速iv KNT009对小鼠自发活动和爬杆能力无明显影响。单次慢速iv KNT009可降低犬收缩压、舒张压、平均动脉压,减慢心率,延长QT间期,使犬呼吸频率减慢,呼吸幅度加大,且均存在量效关系,3 h后上述指标基本恢复正常,加替沙星也有类似变化。结论:KNT009对心血管和呼吸系统有一定的影响,可使血压下降,心率减慢,QT间期延长,呼吸频率减慢,呼吸幅度加大。     

Beagle犬经口给药AF-5/PVP固体分散体9个月和恢复期3周毒性研究

目的研究AF-5对机体产生的中毒反应及其严重程度、主要毒性靶器官以及损害的可逆程度。方法设5、15和50mg/kg,PVP对照组及蒸馏水对照组。按每周给药6次,给Beagle犬经口给予AF-5/PVP共9个月,并经3周恢复期进行毒性研究。结果15和50mg/kg剂量组在给药期间出现血清ALP水平的升高,但是停药后恢复正常;动物体重、进食量、心电图、神经活动状况、尿生化、血液学、以及其他血清生化指标等均未见明显异常。结论血清ALP水平的升高,与经口给予的大剂量的AF-5/PVP固体分散体影响胃肠道有关;Beagle犬经口给药AF-5/PVP固体分散体9个月的无明显毒副反应剂量为5mg/kg。     

Four-week repeated dose oral toxicity study of BMY-28100 in juvenile rats

In order to investigate the repeated dose oral toxicity of BMY-28100 in juvenile rats, the drug was administered orally to 4-day-old Crj: CD(SD) rats of both sexes at daily doses of 250, 750 and 1,500 mg/kg for 4 weeks. The results obtained are summarized as follows: 1. Soiling around the anus apparently correlated to soft stool or diarrhea was observed at 750 and 1,500 mg/kg and the incidence appeared to be dose-related. Three deaths including 1 death due to cannibalization occurred at 750 and 1,500 mg/kg, but they were considered to have been caused by misadministration. 2. Slightly depressed body weight gains were noted in the 750 and 1,500 mg/kg dose groups during early dosing period. 3. Slightly increased averages of food and water consumption observed predominantly in the 1,500 mg/kg dose group at later dosing period and the recovery period were considered as incidental and unrelated to the treatment. 4. Though average values of some blood chemical parameters were slightly suppressed or elevated compared with those of controls at the completion of the dosing and recovery periods, these differences appeared to be generally within normal ranges and to be irrelevant to the drug treatment. No definitive drug-related changes were detected in hematological examinations and urinalyses. 5. The average absolute and/or relative organ weights of the brain, thymus, lungs and liver from male rats in the 1,500 mg/kg dose group were lower than those of the corresponding organs from controls. However, these findings were not considered to be toxicologically significant because no corroborative changes were detected microscopically. 6. Macroscopic and microscopic examinations demonstrated dilatation of the cecum in a dose-related fashion. This phenomenon has been reported with other antibiotics and appears to be drug-related and reversible caused by an alteration of the gut flora. There were no other microscopic changes that were considered to be related to the administration of the drug. 7. Electron microscopic examination revealed no drug-related changes in the liver and kidneys from rats of the 1,500 mg/kg dose group. Based upon these results, the no-effect dose level of BMY-28100 was estimated to be 250 mg/kg/day for both male and female juvenile rats in the 4-week repeated dose oral toxicity study if the finding of cecum dilatation was not considered.(ABSTRACT TRUNCATED AT 400 WORDS)     

A two-year drinking-water study of dichloromethane in rodents. I. Rats

In order to evaluate its toxicity and carcinogenic potential, dichloromethane (DCM) at levels of 0, 0, 5, 50, 125 and 250 mg/kg body weight/day was administered in deionized water to a total of 500 Fischer 344 rats of each sex for 104 wk. An additional group received a level of 250 mg/kg body weight/day for 78 wk followed by a 26-wk recovery period during which only deionized water was presented. Kills were performed at 26-wk intervals. Statistically significant effects on body weight, water consumption and food consumption were observed at the two highest dose levels. Minimal effects were noted on the haematological and serum chemistry parameters monitored. Treatment-related hepatic changes were observed histomorphologically in both sexes after 78 wk of treatment. These changes consisted of an increased incidence of foci/areas of cellular alteration and of fatty change at all dose levels except the lowest. A decrease in the severity of fatty change was observed in the recovery group, but no difference was noted in the incidence of cellular alteration. An increased incidence of hepatic tumours noted in females treated at 50 and 250 mg/kg/day was within the range of historical control incidences. In view of an unusually low incidence of similar tumours in the concurrent control groups and the absence of an increased incidence of hepatic tumours in the group treated at 125 mg/kg/day, the effect seen at 50 and 250 mg/kg/day was not considered to be attributable to DCM treatment. Under the experimental conditions of this study, there was a no-observable-effect level of 5 mg/kg/day in both males and females.     

A repeated 28-day oral dose toxicity study of nonylphenol in rats,based on the ‘Enhanced OECD Test Guideline 407’ for screening of endocrine-disrupting chemicals

A 28-day repeated oral dose toxicity study of nonylphenol (NP) was performed for an international validation of the ‘Enhanced OECD Test Guideline 407’ paying particular attention to the sensitivity of individual endocrine-related parameters. Sprague-Dawley rats, each group consisting of ten males and ten females, were administered NP once daily by gavage at doses of 0 (control), 10, 50, or 250 mg/kg body weight. At 250 mg/kg, three females died or became moribund during the experiment. At this dose, hepatic and renal toxicity was evident in both sexes with increase of relative liver and kidney weights as well as histopathological changes, such as centrilobular liver cell hypertrophy and a variety of renal tubular lesions, and alteration of serum biochemical parameters, some of them being evident from 50 mg/kg in females (glucose and inorganic phosphates). Hematologically, development of anemia was evident at 250 mg/kg in both sexes. Regarding endocrine-related effects, increase of thyroid weight in males was detected from 50 mg/kg. At 250 mg/kg, males exhibited reduction of relative weights of the ventral prostate and seminal vesicles, and females developed irregular estrous cyclicity and vaginal mucosal hyperplasia. Although changes in serum hormone levels were detected in both sexes, magnitude of the changes was small to be regarded as a low toxicological significance. In summary, repeated oral doses of NP to rats for 28 days resulted in hepato-renal toxicity from 50 mg/kg and anemia at 250 mg/kg. Effects on the endocrine system were observed from 50 mg/kg, and assessment of weights and histopathology of endocrine-related organs and estrous cyclicity may be valid in a battery for detecting endocrine effects of NP. The no-observed-adverse-effect level of NP was estimated to be 10 mg/kg per day.     

Pre-clinical toxicity studies on the new nitroimidazole 1-methylsulphonyl-3-(1-methyl-5-nitroimidazole-2-yl)-2- imidazolidinone

Administration of 1-methylsulphonyl-3-(1-methyl-5-nitro-2-imidazole-yl)-2-imidazolidinone (Go 10213) at a dose of 5000 mg/kg to rat, mouse, guinea pig and rabbit and 3000 mg/kg to dog did not induce any toxic symptoms or mortality. Repeated daily gavaging with doses ranging from 50-3000 mg/kg/day were tolerated by rats for 2 weeks. No mortality was noticed in treated animals. Reduction in weight gain was observed in male rats on 2000 mg/kg per day and females on 1000 mg/kg per day. No toxic changes were noticed in dogs treated with 200 mg/kg per day for 2 weeks. One monkey treated with 75 mg/kg per day for 4 weeks tolerated the compound without exhibiting any toxic effects. No drug induced alterations were noticed in rats gavaged with 60 and 200 mg/kg per day for 4 weeks. Rats treated with a daily dose of 600 mg/kg showed reduction in body weight gain and atrophy of testes and these changes were reversible after stopping of medication. Dogs medicated with 30 and 100 mg/kg per day tolerated the drug for 4 weeks. Except slight ataxia in a few dogs treated with 100 mg/kg per day, no other drug induced toxic effects were noticed. Neurological symptoms were noticed in all dogs on high dose of 200 mg/kg. Three animals out of six were sacrificed in extremis in this dose. After discontinuation of Go 10213 all dogs on 100 and 200 mg/kg per day recovered normal gait in about a week. No definitive drug induced changes were noticed in laboratory investigations, gross and histopathological examinations.(ABSTRACT TRUNCATED AT 250 WORDS)     

2-(α-羟基戊基)苯甲酸钾反复给药对大鼠的毒性研究

目的观察Ⅰ类抗脑缺血新药2-(α-羟基戊基)苯甲酸钾[potassium 2-(1-hydroxypentyl)-benzoate,dl-PHPB]反复给药对大鼠的毒性反应。方法SD大鼠,雌、雄各半,根据给药剂量分为10,30,90 mg/kg组及溶剂对照组,尾静脉反复给药30 d,停药后恢复期观察21 d。检测指标包括动物一般状况、体重、进食量、血液常规、血液生化、尿10项和病理组织学检查等。结果 SD大鼠连续静脉注射dl-PHPB 30 d,可剂量依赖性地引起肝脏重轻度增加、血清球蛋白升高、凝血酶时间(TT)延长。30,90 mg/kg剂量组尿潜血阳性及90 mg/kg剂量组尿蛋白升高。这些改变停药后均可恢复。在90 mg/kg剂量、药物质量浓度为45 g/L时,可见明显的血管刺激性,恢复期结束时血管病变仍然存在,但已开始修复。结论SD大鼠静脉注射dl-PHPB 30 d,其无毒反应剂量为30 mg/kg(相当于药效剂量的10倍);90 mg/kg(相当于药效剂量的30倍)时可见轻度毒性反应,主要为可逆性的肝脏、肾脏损伤及血管刺激性。上述研究结果为dl-PHPB的临床安全合理应用提供了参考。     

Hypoglycemic and antihyperglycemic effect of Gmelina asiatica LINN. in normal and in alloxan induced diabetic rats

The hypoglycemic and antihyperglycemic effect of alcoholic extract of root of Gmelina asiatica LINN. (G. asiatica) was investigated in normal and in alloxan induced diabetic rats. The blood glucose levels were measured at 0 h and 1, 2, 4, 6, 8 and 16 h after the treatment. The alcoholic extract of G. asiatica showed significant (p<0.05) dose dependent percentage blood glucose reduction in normal (25.8% at 100 mg/kg, 28.9% at 250 mg/kg and 32.4% at 500 mg/kg body weight) and in diabetic rats (26.6% at 100 mg/kg, 32.1% at 250 mg/kg and 48.2% at 500 mg/kg body weight) respectively at 6 h. The antihyperglycemic effect of G. asiatica was compared with the reference standard drug tolbutamide (40 mg/kg).     

Toxicological studies on isepamicin (HAPA-B). VII. Chronic intramuscular test in the rat

Chronic toxicity in the rat of isepamicin (HAPA-B), a new aminoglycoside antibiotic, was examined in comparison with amikacin (AMK). Daily doses of 3.125, 6.25, 25 and 100 mg/kg of HAPA-B or 25 and 100 mg/kg of AMK were injected intramuscularly for 6 months, and recovery test was carried out for 2 months after discontinuing the drug. No animal died and there were no changes in general symptoms except for hemorrhage of injection sites of both drugs. Decreases in body weight gain and food consumption were observed in 100 mg/kg dose group of either drug. Water consumption was markedly increased in males of the AMK 100 mg/kg dose group during administration and recovery periods. Decreases in erythrocytes, hematocrit and hemoglobin were observed in 100 mg/kg dose group of either drug. These decreases seemed to be due to renal injury. An increase in the number of platelets was also observed. This was likely caused by the hemorrhage at injection sites. These changes persisted into the recovery period. Elevation of BUN was observed in the 100 mg/kg dose group of either drug. Its value in the AMK 100 mg/kg dose group was markedly higher than that in the HAPA-B 100 mg/kg dose group and did not decrease back to the normal values even during the recovery period. An increase of urine volume and a decrease of urine specific gravity were observed in males in the 100 mg/kg group of either drug. Furthermore, NAG was elevated in a dose-dependent manner from 25 mg/kg with both drugs. The weight of kidney increased dose-relatedly and significantly in groups administered with 25 mg/kg or more of either drug and weight of caecum increased dose-relatedly and significantly in groups administered with 6.25 mg/kg or more of HAPA-B or 25 mg/kg or more of AMK. Discoloration and enlargement of the kidney occurred in a dose-dependent manner as observed by necropsy. Eosinophilic granular degeneration, swelling, fatty degeneration, necrosis, calcification in the epithelial cells of the proximal convoluted tubuli, and thickenings of Bowman'S capsule and tubular basement membrane were observed at 25 and 100 mg/kg dose groups of either drug. In recovery periods, after the necrosis disappeared, calcification and regeneration were observed in epithelial cells. Electron microscopic findings showed an increase in the number of large lysosomes containing myeloid bodies in the epithelial cells of the proximal convolute tubuli with either drug.(ABSTRACT TRUNCATED AT 400 WORDS)     

Single dose oral toxicity study of BMY-28100 in juvenile rats and dogs

In order to investigate the single dose oral toxicity of BMY-28100 in juvenile animals, the drug was administered in single doses to 4-day-old and 14-day-old Crj: CD (SD) rats of both sexes at a dose of 2,000 mg/kg, and to 4-week-old beagle dogs of both sexes at doses of 500, 1,000 and 2,000 mg/kg by oral route. The results obtained are summarized as follows: 1. In rats, decreases of the body weight gain were observed for male and female rats treated with the drug on postnatal day 4 through 5 days and 3 days after dosing, respectively. There were no apparent drug-related toxic signs. No deaths occurred during the observation period. Enlargement of the cecum was found in a few rats of both sexes administered the drug on postnatal day 4 or 14. 2. In dogs, watery-mucous diarrhea observed at 2 to 3 hours after dosing in all dose groups was not dose-related. This finding lasted in some dogs till 4 days after dosing. An increased incidence of emesis was induced in all males at 2,000 mg/kg and all females of all dose groups except one female at 2,000 mg/kg. Body weights increased normally for all dogs, but one male at 1,000 mg/kg showed a transient decrease in food consumption. No drug-related histopathological changes were found. Based upon these results, BMY-28100 at 2,000 mg/kg induced no apparent toxic changes in the present experimental conditions. Therefore, the single dose oral toxicity of the drug in juvenile animals appeared to be very slight and generally similar to that in adults.(ABSTRACT TRUNCATED AT 250 WORDS)     

增免胶囊对正常小鼠免疫功能的影响

目的:观察增免胶囊对正常小鼠免疫功能的影响.方法:灌胃给予不同剂最增免胶羹(250 mg/kg,500 mg/kg),观察对小鼠外周血像、免疫器官重量、血清溶血素水平和脾脏淋巴细胞转化指数.结果:对正常小鼠,增免胶囊能增加其外周血白细胞数最和脾脏指数,而对胸腺指数则有降低的趋势,对小鼠脾脏淋巴细胞转化指数有一定的升高.结论:增免胶囊能够增强正常小鼠的免疫功能和造血功能.     

Toxicokinetics of cinnamaldehyde in F344 rats

The toxicokinetic profile of cinnamaldehyde (CNMA) was investigated in Fischer 344 rats. CNMA was found to be unstable in blood. After iv administration, a large fraction of CNMA was immediately oxidized to cinnamic acid. The biological half-life of CNMA after iv administration was found to be 1.7 hr. After administration by gavage of CNMA at 250 or 500 mg/kg body weight using corn oil as vehicle, the maximum blood concentrations of CNMA were in the order of 1 μg/ml. These low blood concentrations were maintained over a 24-hr period after a dose of 500 mg/kg, which is relatively long considering the short (1.7 hr) biological half-life of CNMA. The estimated oral bioavailability of CNMA was less than 20% for both the 250 and 500 mg/kg doses. No CNMA was present in blood at any time in rats dosed with 50 mg CNMA/kg body weight. Only a small amount of the administered CNMA was excreted in rat urine as free cinnamic acid or β-glucuronide-conjugated cinnamic acid. The majority of CNMA administered orallywas excreted in urine as hippuric acid within 24 hr. The maximum excretion rate occurred at 8 hr after gavage. Hippuric acid recovered in 50-hr urine samples was found to be directly proportional to the oral dose of CNMA.