牡荆素在大鼠体内的代谢研究

目的 研究黄酮碳苷牡荆素在大鼠体内的代谢产物,并推测其代谢途径。方法 SD大鼠灌胃给予5 mg·kg^-1牡荆素,收集0~3 h,3~6 h,6~12 h的尿液,采用UPLC-Q-TOF检测尿样中代谢产物。结果 采用Metabolynx XS代谢物分析软件,根据质谱碎片信息对代谢物进行结构鉴定,最终得到3个代谢产物。结论 牡荆素在大鼠尿液中检测得到1个一相代谢产物,2个二相代谢产物,推测牡荆素在大鼠体内主要发生氧化、甲基化和葡萄糖醛酸结合反应,其中葡萄糖醛酸化反应是较强的代谢种类。     

肉桂多次ig给药在肾阳虚大鼠体内的积累和代谢分析

目的 考察肉桂多次ig给予肾阳虚大鼠后,鉴定大鼠肾脏、血液、尿液、粪便中原型成分和代谢产物。方法 采用ip氢化可的松方法制备大鼠肾阳虚模型,造模成功后按照生药量1.35g·kg^-1·d^-1ig肉桂提取物,连续15d。末次给药后,收集大鼠血浆、尿液、粪便和肾组织样品,进行UPLC-LTQ-Orbitrap-MS分析。根据色谱保留时间、精确相对分子质量、多级质谱碎片信息结合文献报道对各样本中的成分进行确认,并推测代谢物的代谢途径。结果 从肾阳虚模型大鼠各样本中共鉴定出24个成分,其中3个原型成分,21个代谢产物,包括12个原花青素类、8个木脂素类、2个二萜类、2个有机酸。结论 肉桂成分在肾阳虚大鼠体内代谢广泛,代谢途径主要包括甲基化、硫酸化和葡萄糖醛酸化反应。尿液中检出的化学成分最多,其次为血液、肾组织、粪便。长期给药情况下以原型存在于靶器官和血中成分很少,推测代谢物发挥药效的可能性较大。     

基于UHPLC-HRMS血清代谢组学研究黄芪发酵菌质干预高尿酸血症的作用机制

目的 基于UHPLC-HRMS血清代谢组学研究黄芪发酵菌质对高尿酸血症模型大鼠血清内源性代谢产物的影响及机制。方法 将SD大鼠随机分为空白组、模型组、苯溴马隆组(20 mg·kg^-1)和黄芪发酵菌质高剂量组(3.0 g·kg^-1)、低剂量组(1.5 g·kg^-1)。模型组和各给药组均先采用大鼠灌胃300 mg·kg^-1氧嗪酸钾建立高尿酸血症模型,造模后1 h给药组给予相应药物进行干预,14 d后采集大鼠血清。利用UHPLC-HRMS对不同组别大鼠血清中的内源性代谢产物进行分析,并结合多元数据统计分析方法筛选差异代谢物和代谢通路。结果 造模14 d后高尿酸血症大鼠模型建立成功,黄芪发酵菌质显示出良好的降尿酸作用。与空白组相比,模型组发现了17个与高尿酸血症发病相关的潜在生物标志物;黄芪发酵菌质可显著回调其中10个潜在生物标志物,并主要涉及鞘脂代谢、嘧啶代谢、色氨酸代谢、泛酸和辅酶A生物合成、甘氨酸、丝氨酸和苏氨酸代谢等通路发挥降尿酸作用。结论 本研究可为揭示黄芪发酵菌质降尿酸作用机制研究提供依据,并为黄芪的深度开发利用奠定基础。     

不同剂量染料木黄酮及其代谢产物在大鼠胆汁中的排泄动力学

目的研究不同剂量染料木黄酮及其葡糖醛酸化代谢产物在大鼠胆汁内的排泄动力学。方法将染料木黄酮制成混悬液，分别按6.25，12.5和50 mg·kg^-1给大鼠灌胃，于灌胃后不同时间收集胆汁，用葡糖醛酸酶溶液处理胆汁。采用高效液相色谱法测定胆汁中染料木黄酮及其葡糖醛酸化代谢产物的浓度。结果3种剂量6.25，12.5和50 mg·kg^-1分别给药后，累积以原形从胆汁排泄的药物分别为(42.56±6.54)，(75.17±18.87)和(126.60±34.78) μg，累积经胆汁排泄的总药物(原形药物+葡糖醛酸化药物)分别为(108.46±35.23)，(423.46±158.31)和(853.74±320.84) μg，葡糖醛酸化代谢产物分别占胆汁排泄总量(原形药物+葡糖醛酸化药物)的60.76%，82.25%和85.17%。结论染料木黄酮在大鼠胆汁中主要以葡糖醛酸结合形式排泄，原形药物及其葡糖醛酸化代谢产物在大鼠胆汁中的排泄呈现明显的非线性剂量依赖性特征。     

异欧前胡素在大鼠体内代谢产物的UHPLC-HRMS鉴定分析

目的 分析鉴定异欧前胡素在正常大鼠体内的代谢产物。方法 大鼠灌胃给药后,收集正常组和给药组大鼠的血浆、尿液和粪便样本,并以固相萃取柱提纯生物样品。采用UHPLC-HRMS(Q-Exactive Orbitrap MS)高分辨质谱对生物样品进行分析,并对代谢产物筛选鉴定。结果 在正、负离子模式下,根据所获得的精确分子质量、色谱保留行为、质谱裂解规律、特征碎片离子、对照品比对以及文献报道,最终分析鉴定了32个代谢产物。其代谢途径主要包括呋喃环开环、内酯水解、氧化、甲基化、葡萄糖醛酸化、硫酸酯化以及它们的复合反应。其中,葡萄糖醛酸化产物为首次发现。结论 本研究较为全面地阐明了异欧前胡素在正常大鼠体内的代谢转化情况,可为其进一步的药效学研究提供依据,并为呋喃香豆素类物质的代谢产物分析提供借鉴。     

丹酚酸B对自发性糖尿病大鼠合并大血管病变的保护作用

摘 要 目的：探讨丹酚酸B对自发性糖尿病（GK）大鼠合并大血管病变的保护作用及可能的机制。方法: 将32只GK大鼠随机分为模型组和丹酚酸B低、中、高剂量组(40,80,160 mg·kg^-1),另选取正常8只Wistar大鼠作为正常对照组。所有GK大鼠给予高糖、高脂饲料16周后以L-N-硝基甲酯（L-NAME）10 mg·kg^-1·d^-1灌胃,连续8周。给药开始及结束前对大鼠的血糖和血压进行检测,麻醉后取腹主动脉血进行血常规检测,放血后取胸主动脉制作病理切片,观察血管病变,Western-blot法检测血管内皮细胞生长因子（VEGF）的表达。结果: 所有GK大鼠血糖水平持续升高,但模型组与给药组差异无统计学意义（P>0.05）,模型组大鼠实验结束时血压显著升高,给予丹酚酸B可剂量依赖性降低血压,差异有统计学意义（P＜0.05）;丹酚酸B可显著降低模型大鼠的白细胞总数和分类计数,明显减轻血管病变程度并减少VEGF的表达。结论:丹酚酸B对自发性糖尿病大鼠的大血管具有明显的保护作用,其可能的机制为降低血压、抗炎以及降低VEGF的表达。     

LC-MS/MS鉴定木兰花碱在大鼠体内外主要代谢产物

目的 研究木兰花碱在大鼠体内外的主要代谢产物及代谢途径。方法 SD大鼠ig木兰花碱（50 mg/kg）,收集0~24 h尿液和粪便,0~6 h胆汁以及1、2、4、6、8 h血浆;体外代谢采用肝微粒体温孵系统和肠菌培养液。利用LC-MS/MS对生物样品中的原型药及代谢产物进行鉴定。采用Agilent TC-C₁₈色谱柱（150 mm×4.6 mm,5 μm）,以乙腈-0.1%甲酸水溶液为流动相梯度洗脱,体积流量1.0 mL/min,柱温30℃。质谱采用电喷雾电离源（ESI）,正离子采集模式;扫描范围m/z100~1 000。根据药物体内代谢规则,结合木兰花碱的色谱保留时间和多级质谱碎片离子特征,推测其代谢产物的结构。结果 给药后生物样品中共鉴定出12个代谢产物,其中Ⅰ相代谢产物8个,Ⅱ相代谢产物4个。主要的代谢途径为羟基化、去甲基化、脱氢作用、酮基化、葡萄糖化、葡萄糖醛酸化及硫酸酯化。结论 木兰花碱在体内可发生Ⅰ相和Ⅱ相代谢,肠道菌群和肝药酶可催化木兰花碱发生Ⅰ相代谢转化,Ⅱ相代谢存在于肠道以外部位,最有可能的部位是肝脏。     

HPLC-ESI/MS分析5-羟基黄酮在大鼠体内的代谢产物

目的研究5-羟基黄酮在大鼠体内的代谢产物。方法应用高效液相色谱-电喷雾质谱(HPLC-ESI/MS)检测大鼠灌胃5-羟基黄酮后血浆、尿液、胆汁和粪便中的代谢产物。实验采用Zorbax C18色谱柱,0.05%甲酸乙腈-0.05%甲酸水二元线性梯度洗脱进行色谱分离,并与电喷雾质谱联用,根据正离子模式的分子离子峰获得化合物分子量信息,推测化合物的可能结构。结果仅在大鼠粪便中检测到原形成分,在大鼠尿液、粪便、血浆、胆汁中检测到5-羟基黄酮葡糖醛酸结合物。结论 5-羟基黄酮吸收差,在大鼠体内主要以II相代谢产物葡萄糖醛酸结合物的形式存在。     

UPLC-Q-Exactive Plus Orbitrap-MS鉴定桑色素在大鼠体内的代谢产物

目的 利用UPLC-Q-Exactive PlusSOrbitrap-MS技术对大鼠灌胃给予桑色素后体内的的主要代谢产物进行研究。方法 大鼠灌胃给予桑色素20 mg/kg后,分别收集血浆、尿液和粪便样品,采用超高压液相色谱串联高分辨质谱技术测定桑色素的体内代谢物。结果 根据一级质谱分子离子信息和二级质谱碎裂离子信息,在大鼠血浆和尿液中均发现2个葡萄糖醛酸代谢产物,在粪便中发现脱氢产物。结论 桑色素在大鼠体内的主要代谢途径为葡萄糖醛酸化反应。本研究初步阐明了桑色素在大鼠体内的代谢情况,为进一步药理作用机制研究提供依据。     

格列吡嗪和格列本脲对氯沙坦药动学的影响

目的 研究格列吡嗪和格列本脲对氯沙坦在大鼠体内药动学的影响。方法 将15只大鼠随机分成对照组、格列吡嗪组和格列本脲组,分别灌胃给予0.5% CMC、10 mg·kg^-1格列吡嗪和10 mg·kg^-1格列本脲,0.5 h后灌胃给予5 mg·kg^-1氯沙坦钾,经尾静脉予不同时间点采集血样,采用HPLC测定血样中氯沙坦及其代谢产物E-3174的浓度。采用DAS计算各组主要的药动学参数,并进行统计学分析。结果 合用格列吡嗪后,氯沙坦和E-3174的AUC、MRT和峰浓度均明显增加,氯沙坦的清除率减小;合用格列本脲后,氯沙坦的达峰时间提前,E-3174的MRT延长。结论 与同剂量的格列本脲相比,格列吡嗪对氯沙坦及其代谢产物在大鼠体内的药动学影响较大。临床上合用氯沙坦和格列吡嗪时,应注意潜在的药物相互作用所致的药物不良反应。     

鉴定大鼠注射绿原酸后体内的代谢产物

绿原酸为多种中药注射液的主要成分, 本文采用超高效液相色谱-四极杆飞行时间质谱法 (UPLC/Q- TOF MS) 鉴定大鼠注射给予绿原酸后胆汁、尿、粪和血浆中的代谢产物。利用碰撞能量梯度 (MS^E) 和质量亏损过滤 (MDF) 技术, 在大鼠胆汁、尿、粪和血浆中共检测到35种代谢产物。胆汁中主要代谢产物为O-甲基绿原酸谷胱甘肽结合物, 其排泄量超过胆汁中全部代谢物的80%, 尿中主要为原形、O-甲基结合物、水解代谢产物及葡糖醛酸结合物, 粪中主要为O-甲基结合物及其半胱氨酸结合物, 血浆中主要为原形化合物。绿原酸及其代谢产物经尿和粪便排泄比例相近。实验结果表明, 绿原酸在大鼠体内代谢广泛, 主要途径之一是与谷胱甘肽结合, 提示绿原酸的烯酮双键具有亲电性, 可能与蛋白的巯基共价结合, 导致过敏性不良反应, 应予以关注。     

10-羟基癸烯酸在动物体内吸收、分布、代谢和排泄

10-癸基癸烯酸(即10-HDA,定位标记为³H-10HDA),经小鼠和大鼠口服后,胃肠道吸收快,峰时均在1h,全身分布迅速广泛,与组织亲和力强,肝中放射性为最高,依次为肾、胰、脂肪、脑、脾、心和肺。平均Vd为9.71/kg。Ig和iv的T1/2β在12.6～22.7h。体内消除较缓慢,31 d内,尿粪中放射性累计排泄分别为给药量的85.4%和13.5%,提取尿和胆汁经分析结果主要以原形药物排出。血浆蛋白结合率为63%。血中放射—性时间曲线符合开放二室模型。     

Absorption,distribution, metabolism and excretion of gemigliptin,a novel dipeptidyl peptidase IV inhibitor,in rats

Abstract

1.?The absorption, distribution, metabolism and excretion of a novel dipeptidyl peptidase IV inhibitor, gemigliptin, were examined following single oral administration of ¹⁴C-labeled gemigliptin to rats.

2.?The ¹⁴C-labeled gemigliptin was rapidly absorbed after oral administration, and its bioavailability was 95.2% (by total radioactivity). Distribution to specific tissues other than the digestive organs was not observed. Within 7 days after oral administration, 43.6% of the administered dose was excreted via urine and 41.2% was excreted via feces. Biliary excretion of the radioactivity was about 17.7% for the first 24?h. After oral administration of gemigliptin to rats, the in vivo metabolism of gemigliptin was investigated with bile, urine, feces, plasma and liver samples.

3.?The major metabolic pathway was hydroxylation, and the major circulating metabolites were a dehydrated metabolite (LC15-0516) and hydroxylated metabolites (LC15-0635 and LC15-0636).     

丹酚酸B镁对兔急性心梗再灌注后无复流心肌损伤的保护作用

目的 评价丹酚酸B镁（salvianolic acid B,Sal-B）对兔急性心肌梗死再灌注后心肌损伤的保护作用。方法 新西兰大白兔40只随机分成4组,即假手术组、心肌缺血再灌注（myocardial ischemia/reperfusion,MI/R）、再灌注低剂量组（Sal-B20 mg·kg^-1组）、再灌注高剂量组（Sal-B 60 mg·kg^-1组）,每组10只。假手术组只开胸不结扎,其余3组结扎左室缘支90 min,切断结扎线120 min,建立MI/R模型。各组分别于结扎左心室缘支前5 min、结扎后90 min、再灌注120 min时取血,检测肌酸激酶同工酶（CK-MB）、心肌肌钙蛋白I （cTnI）,并评估缺血范围、无复流范围及梗死区心肌范围。结果 结扎90 min后,MI/R组、Sal-B 20 mg·kg^-1组和Sal-B 60 mg·kg^-1组3组之间CK-MB、cTnI水平差异无统计学意义。再灌注120 min后,Sal-B 60 mg·kg^-1组的血清CK-MB、cTnI水平显著低于MI/R组、Sal-B 20 mg·kg^-1组,差异有统计学意义（P<0.05）。各组染色所测的冠脉结扎区心肌缺血范围基本一致。与MI/R组、Sal-B 20 mg·kg^-1组比,Sal-B 60 mg·kg^-1组可以显著减少无复流面积（P<0.05）和梗死面积（P<0.05）,MI/R组和Sal-B 20 mg·kg^-1组之间差异无统计学意义。结论 Sal-B 60 mg·kg^-1能在一定程度上减轻心肌细胞结构损伤,缩小心肌梗死面积,减轻无复流的发生。     

Excretion of [3H]triptolide and its metabolites in rats after oral administration

Aim： To investigate the routes of elimination and excretion for triptolide recovered in rats.
Methods： After a single oral administration of [3H]triptolide （0.8 mg/kg, 100 μCi/kg） in Sprague Dawley rats, urine and fecal samples were collected for 168 h. To study biliary excretion, bile samples were collected for 24 h through bile duct cannulation. Radioactivity was measured using a liquid scintillation analyzer, and excretion pathway analysis was performed using an HPLC/on-line radioactivity detector.

Results： The total radioactivity recovered from the urine and feces of rats without bile duct ligation ranged from 86.6%–89.1%. Most of the radioactivity （68.6%–72.0%） was recovered in the feces within 72 h after oral administration, while the radioactivity recovered in the urine and bile was 17.1%–18.0% and 39.0%–39.4%, respectively. The HPLC/on-line radiochromatographic analysis revealed that most of the drug-related radioactivity was in the form of metabolites. In addition, significant gender differences in the quantity of these metabolites were found： monohydroxytriptolide sulfates were the major metabolites detected in the urine, feces, and bile of female rats, while only traces of these metabolites were found in male rats.

Conclusion： Radiolabeled triptolide is mainly secreted in bile and eliminated in feces. The absorbed radioactivity is primarily eliminated in the form of metabolites, and significant gender differences are observed in the quantity of recovered metabolites, which are likely caused by the gender-specific expression of sulfotransferases.     

Metabolism and excretion of CP-122,721, a non-peptide antagonist of the neurokinin NK1 receptor,in dogs: Identification of the novel cleaved product 5-trifluoromethoxy salicylic acid in plasma

The metabolism and excretion of a potent and selective substance P receptor antagonist, CP-122,721, have been studied in beagle dogs following oral administration of a single 5?mg?kg^?1 dose of [¹⁴C]CP-122,721. Total recovery of the administered dose was on average 89% for male dogs and 95% for female dogs. Approximately 94% of the radioactivity recovered in urine and feces was excreted in the first 72?h. Male bile duct-cannulated dogs excreted a mean of ～56% of the dose in bile, ～11% in feces, and ～25% in urine. The sum of radioactivity in bile and urine indicates >80% of the [¹⁴C]CP-122,721-derived radioactivity was absorbed by the gastrointestinal tract. CP-122,721 was extensively metabolized in dogs, and only a small amount of parent CP-122,721 was excreted as unchanged drug. There were no significant gender-related quantitative/qualitative differences in the excretion of metabolites in urine or feces. The major metabolic pathways of CP-122,721 were O-demethylation, aromatic hydroxylation, and indirect glucuronidation. The minor metabolic pathways included: Aliphatic oxidation at the piperidine moiety, O-dealkylation of the trifluoromethoxy group, and N-dealkylation with subsequent sulfation and/or oxidative deamination. In addition, the novel cleaved product 5-trifluoromethoxy salicylic acid (TFMSA) was identified in plasma. These results suggest that dog is the most relevant animal species in which the metabolism of CP-122,721 can be studied for extrapolating the results to humans.     

UPLC-MS/MS测定地西泮对大鼠CYP450酶活力的影响

目的 基于UPLC-MS/MS同时测定大鼠血浆中的5种探针药物（安非他酮、美托洛尔、咪达唑仑、非那西丁和甲苯磺丁脲）,5种探针药物分别是细胞色素P450同工酶CYP2B6,CYP2D6,CYP3A4,CYP1A2和CYP2C9底物,评价地西泮对大鼠细胞色素P450酶活性影响。方法 将大鼠随机分成地西泮低剂量组（1 mg·kg^-1）、高剂量组（5 mg·kg^-1）和对照组。地西泮低剂量组、高剂量组腹腔注射地西泮10 d,对照组腹腔注射生理盐水10 d。5种探针药物通过灌胃给予大鼠,用UPLC-MS/MS测定血浆药物浓度。结果 与对照组相比,地西泮组安非他酮、美托洛尔和非那西丁药动学参数均有统计差异。地西泮组安非他酮、非那西丁的AUC比对照组高,但美托洛尔AUC比对照组低。结论 地西泮可能会抑制大鼠CYP2B6酶活性,抑制CYP1A2酶活性,诱导大鼠CYP2D6酶活性,而对大鼠CYP3A4、CYP2C9酶活性无影响。     

痛风康宁片对高尿酸血症的预防作用及机制研究

目的 采用多种实验模型评价痛风康宁片（TKT）对高尿酸血症的预防作用并研究其作用机制。方法 采用ig酵母膏联合ip氧嗪酸钾法制备大鼠高尿酸血症模型,酵母膏（20 g·kg^-1）连续ig 7 d,且于ig酵母膏第5天开始给药,设置对照组、模型组和 TKT 低、中、高（0.58、1.15、2.30 g·kg^-1）组和苯溴马隆 27 mg·kg^-1组,对照及模型组给予等容量 0.5%CMC-Na,每天 ig给药 1次,给药第 3天（即 ig酵母膏第 7天）,ip注射氧嗪酸钾 200 mg·kg^-1造模。检测注射氧嗪酸钾后 2、4 h的血清尿酸浓度、尿量、尿液中尿酸排出量及肾脏中尿酸盐转运体 1（URAT1）、有机阴离子转运体 1（OAT1）、OAT3抗体表达,评价TKT对大鼠高尿酸血症的预防作用;采用次黄嘌呤诱导小鼠高尿酸血症模型,设置对照组、模型组和TKT低、中、高剂量（0.83、1.66、3.33 g·kg^-1）组及苯溴马隆 39 mg·kg^-1组,每天 ig给药 1次,连续给药 5 d,对照及模型组给予等容量0.5% CMC-Na,检测血尿酸、尿酸酶及黄嘌呤氧化酶（XOD）含量,评价TKT对小鼠高尿酸血症的预防作用;采用大鼠水负荷模型,设置对照组和TKT低、中、高（0.58、1.15、2.30 g·kg^-1）组及氢氯噻嗪27 mg·kg^-1组,每天ig给药1次,连续给药 3 d,对照组给予等容量 0.5% CMC-Na,通过检测给药后 1、2、3、4、5 h 的尿量及给药后 5 h 内总尿量,评价TKT 对大鼠的利尿作用。结果 与模型组比较,TKT（0.58、1.15、2.30 g·kg^-1）能明显降低大鼠血清尿酸浓度（P＜0.05、0.01）,明显增加尿酸排出量（P＜0.05、0.01）,明显增加肾脏OAT1的表达（P＜0.05、0.01）,1.15、2.30 g·kg^-1能明显减少肾脏 URAT1 的表达 （P＜0.05、 0.01）; TKT （1.66、 3.33 g·kg^-1） 能明显降低小鼠血清尿酸浓度 （P＜0.05、 0.01）,TKT（0.83、1.66、3.33 g·kg^-1）能明显增加尿酸酶含量（P＜0.05、0.01）;TKT（0.58、1.15、2.30 g·kg^-1）能明显增加给药后不同时间点的尿量（P＜0.05、0.01）,明显增加给药后5 h总尿量（P＜0.05、0.01）。结论 TKT通过促进尿酸分泌、抑制尿酸重吸收及利尿作用,使血清尿酸浓度明显降低、尿尿酸排出量明显增加,显示对实验性高尿酸血症有明显的预防作用。     

Absorption,Distribution, Metabolism,and Excretion of N-Octylbicycloheptene Dicarboximide (MGK 264) Administered Orally to Rats

Abstract

Experiments were conducted in four groups of rats to determine the absorption, distribution, metabolism, and excretion (ADME) patterns following oral administration of [hexyl-1-¹⁴C] N-octylbicycloheptene dicarboximide (MGK 264).

Ten rats (five males and five females) were used in each of the four experiments. Fasted rats were administered fhexyl-1-¹⁴C] MGK 264 at a single oral dose of 100 mg/kg, at a single oral dose of 1000 mg/kg, and at a daily oral dose of 100 mg/kg of nonradiolabeled compound for 14 days followed by a single dose of ¹⁴C-labeled compound at 100 mg/kg. Rat blood kinetics were determined in the fourth group following a single oral dose of 100 mg/kg. Each animal was administered 18-30 μCi radioactivity.

Urine and feces were collected for all groups at predetermined time intervals. Seven days after dose administration, the rats were euthanized and selected tissues and organs were harvested. Samples of urine, feces, and tissues were subsequently analyzed for ¹⁴C content.

In the blood kinetics study, radioactivity peaked at approximately 4 h for the males and 6 h for the females. The decline of radioactivity from blood followed a monophasic elimination pattern. The half-life of blood radioactivity was approximately 8 h for males and 6 h for females.

Female rats excreted 71.45-73.05% of the radioactivity in urine and 20.87-25.28% in feces, whereas male rats excreted 49.49-63.49% of the administered radioactivity in urine and 31.76-46.67% in feces. Total tissue residues of radioactivity at 7 days ranged from 0.13 to 0.43% of the administered dose for all dosage regimens. The only tissues with ¹⁴C residues consistently higher than that of plasma were the liver, stomach, intestines, and carcass. The total mean recovered radioactivity of the administered dose in the studies ranged between 93.1 and 97.4%. No parent compound was detected in the urine.

Four major metabolites and one minor metabolite were isolated from the urine by high-performance liquid chromatography (HPLC) and identified by gas chromatography/mass spectometry (GC/MS) and liquid chromatography/mass spectrometry (LC/MS). The four major metabolites were shown to be carboxylic acids produced by either ω-1 oxidation or β-oxidation of the side chain and oxidation of the norbornene ring double bond. The minor metabolite was the carboxylic acid of the intact norbornene ring.

The gender of the animals affected the rate, route of excretion, and metabolic profile. The urinary excretion rate was faster in females than in males and the amount excreted was also greater in female rats.