紫杉醇纳米乳剂的体内外考察

目的考察紫杉醇纳米乳剂的形态、粒径分布及急性过敏反应,研究紫杉醇注射剂及自制紫杉醇纳米乳剂在大鼠体内的药代动力学。 方法用HPLC法测定大鼠体内紫杉醇含量。数据用3P87处理,得到各主要药代动力学参数。 结果纳米乳剂平均粒径为17.2 nm。纳米乳剂急性过敏反应为阴性,而市售紫杉醇注射液急性过敏反应为阳性。血浆中杂质及制剂中辅料不干扰紫杉醇的测定。大鼠iv自制紫杉醇纳米乳剂及紫杉醇注射液后的药-时曲线均符合二室模型。数据用3P87处理,得到各主要药代动力学参数。纳米乳剂及注射液的k₁₀分别为0.57,1.29·h^-1,k₁₂分别为1.44,1.27·h^-1,k₂₁分别为3.08,0.51·h^-1,AUC分别为34.98,21.85 mg·h·L^-1。结论紫杉醇纳米乳剂较紫杉醇注射液毒性降低,可在一定程度上延长药物在大鼠体内的循环时间。     

定量评价去氢骆驼蓬碱注射用乳剂的组织靶向性

目的：定量评价静脉注射用乳剂作为药物载体给药后对主要脏器的靶向性并对给药系统靶向性的定量评价参数进行讨论和评价。方法：用3H标记的去氢骆驼蓬碱(harmine,HAR)分别制成静脉注射乳剂、水溶液和脂质体,经小鼠静脉注射后测定主要脏器组织中的总放射性强度,计算重量-平均总靶向性系数Te^*和靶向性系数Te,并对乳剂的靶向性意义作出定量评价。结果：静脉乳剂可显著提高放射性在肝、脾、淋巴器官的分布,降低放射性向脑组织的转运。结论：静脉注射乳剂是一很有意义的靶向给药系统,重量-平均总靶向性系数Te^*是较全面的靶向性评价参数。     

克林沙星在大鼠体内的药代动力学和生物利用度

目的　研究克林沙星在大鼠体内的药动学和生物利用度。方法　HPLC法测定大鼠ig和iv克林沙星后的血药浓度,计算药动学参数和生物利用度。色谱柱为C₁₈柱(5μm),流动相为乙腈-0.05mol·L^-1柠檬酸三乙胺液(pH2.5)(20∶80),流速为1.0mL·min^-1,检测波长300nm。结果　克林沙星0.1-20μg·mL^-1呈良好线性关系,在大鼠体内的药动学过程符合一室模型,大鼠ig50和100mg·kg^-1后,C_max和AUC均与剂量呈正比,T_1/2与剂量无关;绝对生物利用度(F)为42%。结论　克林沙星50-100mg·kg^-1的吸收和消除呈一级动力学特征,在大鼠体内的生物利用度低。     

HPLC测定大鼠血浆中雪胆甲素的浓度及其药动学研究

摘 要 目的： 建立灵敏、快捷测定大鼠血浆中雪胆甲素浓度的高效液相色谱法(HPLC),并应用于体内药动学特征研究。方法: 色谱条件：色谱柱：Dikma Diamonsil C₁₈(250 mm×4.6 mm, 5 μm),流动相：乙腈∶水(45∶55 ,v/v),检测波长: 212 nm,柱温: 35℃,流速: 1.0 ml·min^-1。采取大鼠静脉注射给药途径,于不同时间点采血测定血浆药物浓度,并用DAS2.0计算药动学参数。结果: 雪胆甲素血药浓度在0.146～ 14.060 μg·ml^-1范围内线性关系良好（r=0.999 3）;方法回收率为99.02% ～104.22%;提取回收率为84.74%～86.80%;日内、日间精密度RSD均＜5%,稳定性考察符合要求。应用此法测定大鼠尾静脉注射给药后的血药浓度并计算主要药动学参数,1.0,2.0,4.0 mg·kg^-1三个剂量组静脉给药后在大鼠体内均符合三室模型,主要药动学参数分别为t_1/2β(h):0.732±0.151,0.681±0.055,0.667±0.064; Vd(L·kg^-1):0.147±0.089, 0.131±0.095,0.153±0.047; CL(L·h^-1·kg^-1): 0.287±0.031,0.304±0.063, 0.318±0.029和AUC_0→∞(mg·h·L^-1): 3.646±1.124, 4.916±1.227,9.385±1.419。结论:该法快速、简便、准确,符合生物样品测定需求,可用于药动学研究。雪胆甲素静脉注射给药后在体内呈三室模型,代谢较快,具有线性动力学特征。     

基于UPLC-MS/MS的新型脂肪酸合成酶抑制剂4k在大鼠体内的药动学研究

目的 建立超高效液相色谱-串联质谱法(UPLC-MS/MS)测定大鼠血浆中新型脂肪酸合成酶抑制剂4k的浓度,并研究其在大鼠体内的药动学特征。方法 12只SD大鼠随机分为2组,分别单次尾静脉注射和灌胃给予4k。以三氯生为内标,建立并验证UPLC-MS/MS测定不同时间点大鼠血浆中4k的浓度,用DAS 2.0软件计算药动学参数。结果SD大鼠单次静脉注射后主要药动学参数为T_1/2 (0.54±0.39)h,T_max 0.033 h,C_max (2 730.72±803.13)ng·mL^-1,AUC_0-∞ (577.72± 174.58)ng·mL^-1·h,Vd (1 241.17±657.98)mL·kg^-1,CL (1 882.67±610.03)mL·kg^-1·h^-1,MRT_0-∞ (0.42±0.19)h。由于灌胃给药后,大鼠体内血药浓度低于定量下限,因此无法进行药动学参数计算。结论 本方法简单准确、快速灵敏,适用于大鼠血浆中4k浓度的测定及其药动学研究。     

柱前衍生-HPLC测定白消安在家兔体内的药动学参数

目的 建立测定家兔血清中白消安浓度和家兔体内药动学特征的柱前衍生化HPLC。方法 以1,5-戊二醇二甲磺酸酯为内标,二乙基二硫代氨基甲酸钠为衍生化试剂。流动相：甲醇-水（54∶46）,流速：0~20 min（1.0 mL·min^-1）,20~27 min（1.3 mL·min^-1）。柱温：30℃,检测波长：280 nm,进样量：25 μL。家兔分别以灌胃、静注的方式给予白消安,按本法测定血药浓度,DAS 3.0计算药动学参数。结果 白消安的血药浓度在0.1~3.4 mg·-L¹ 内线性关系良好（r=0.999 7）,日内、日间精密度以及样品稳定性符合中国药典2015年版的规定。低、中、高浓度的萃取回收率分别为90.0%,89.0%,91.5%。不同给药途径获得的药动学参数：单剂量口服t_1/2=（2.26±0.66）h,k=（0.33±0.12）·h^-1,k_a=（2.54±1.3）·h^-1,AUC_0–t=（1.95±0.18）h·mg·mL^-1;单剂量静脉注射t_1/2=（1.53±0.09）h,k=（0.45±0.03）·h^-1,AUC_0–∞=（4.38±0.26）h·mg·mL^-1。多剂量口服后C_ss=（0.48±0.03）mg·mL^-1,AUC_0–τ=（3.87±0.26）h·mg·mL^-1。结论 建立的柱前衍生-HPLC法适用于白消安血药浓度测定及药动学研究,不同给药途径的药动学参数为临床药动学研究提供了依据。     

丹参酮ⅡA对茶碱在大鼠体内药动学特征的影响

目的 研究丹参酮ⅡA对大鼠体内茶碱药动学特征的影响。方法 将24只大鼠随机分成3组,Ⅰ组：生理盐水,ip×7 d;Ⅱ组：丹参酮ⅡA 7 mg·kg^-1·d^-1,ip×7 d;Ⅲ组：丹参酮ⅡA 20 mg·kg^-1·d^-1,ip×7 d。于第7天给药后3组均灌胃给予氨茶碱(20.8 mg·kg^-1),分别于给药前后的0.17,0.33,0.5,1.0,1.5,2.0,4.0,6.0,8.0,10.0,12.0 h尾静脉采血。用HPLC测定血浆中茶碱的血药浓度,并用DAS计算药动学参数。结果 茶碱在大鼠体内主要药动学参数,C_max为(29.43±1.53)mg·L^-1、AUC_0→∞为(156.95±10.22)mg·h·L^-1、MRT_0-∞为(4.44±0.42)h、CLz/F为(0.13± 0.01)L·h^-1·kg^-1。与Ⅰ组比较,Ⅱ组各参数无显著性差异,Ⅲ组主要参数AUC_0→12h、AUC_0→∞、C_max、MRT_0-t、MRT_0-∞、CLz/F等有显著性差异(P<0.05),其中C_max、AUC_0→∞分别下降了7.54%和14.69%,CLz/F增加了23.08%。结论 高剂量的丹参酮ⅡA能影响茶碱在大鼠体内药动学特征,而低剂量无影响。     

LC-MS/MS测定大鼠血浆中K15的浓度及其在药动学研究中的应用

目的 建立SD大鼠血浆中（3AS,4S,6AR）-四氢-4-甲氧基-呋喃并[3,4-B]呋喃-2（3H）-酮（K15）的LC-MS/MS测定方法,并进行K15的药动学研究。方法 分别灌胃及静脉注射给予大鼠不同剂量K15后,从眼眶静脉丛取血,并采用LC-MS/MS测定大鼠血浆中K15的浓度变化。利用DAS药动学软件拟合主要药动学参数AUC、C_max、T_max、T_1/2等。结果 大鼠血浆中的内源性杂质不干扰K15的测定,日内精密度4.53%~6.60%,日间精密度5.19%~8.14%,准确度为96.10%~102.49%。K15的线性范围为25~1 000 ng·mL^-1,r=0.998 5。K15的定量下限为25 ng·mL^-1（RSD=12.7%,n=6）。150,450和1 000 mg·kg^-1灌胃给药的生物利用度分别为79.5%,44.4%和57.0%。结论 该方法适用于K15在大鼠中的药动学研究。K15在大鼠中的药动学为非线性动力学,灌胃给予大鼠后在其体内具有一定的系统暴露量,但没有随给药剂量呈线性增加。在给药剂量为100和450 mg·kg^-1时,其在体内的C_max没有显著性增高,但是在1 000 mg·kg^-1时,C_max显著增加。随着给药剂量的增加,K15在大鼠体内的T_1/2显著增加,提示K15在大鼠体内的暴露时间随剂量的增加显著延长。     

金黄色葡萄糖球菌肠毒素C2改构蛋白大鼠药动学研究

目的 研究金黄色葡萄糖球菌肠毒素C2改构蛋白（2M-118）在大鼠体内单次和多次给药后的药动学特征。方法 24只大鼠随机分为3组,每组8只,雌雄各半,分别单次iv低、中和高剂量（1、2和4 mg/kg）2M-118,高剂量组大鼠于单次给药后,继续每天给药1次,共给药8次。于给药前（0 h）,首次及末次给药后5、10、20、30、45 min和1.0、1.5、2.0、4.0、6.0、8.0 h采集眼静脉丛全血约0.5 mL,制备血清。采用双抗体夹心酶联免疫吸附测定（ELISA）法检测大鼠血清药物浓度,采用DAS 3.2.8药动程序计算药动学参数。结果 大鼠单次iv 2M-118后,在1～4 mg/kg剂量内,峰浓度（C_max）、初始浓度（C₀）和药时曲线下面积（AUC）均与剂量呈正相关;消除相半衰期（t_1/2Z）随剂量递增明显延后,平均t_1/2z分别为0.24、0.60和1.18 h;表观分布容积（V_z）随剂量递增而增大;各剂量组的清除率（CL_z）较为一致。与同剂量（4 mg/kg）单次给药相比,大鼠多次给药后的主要药动学参数基本保持一致,体内药物无蓄积倾向。结论 大鼠单次iv 2M-118后,在1～4 mg/kg剂量内,体内暴露量与剂量呈正相关,其清除可能呈现非线性动力学特征;单次与多次iv给予相同剂量2M-118后,药动学行为特征基本一致,无明显药物蓄积。     

莫达非尼在小鼠体内的药动学-药效学联合研究

对莫达非尼 (modafinil, MOD) 在小鼠体内的药动学和药效学进行联合研究, 以阐明其关联性, 为临床合理用药提供依据。以莫达非尼120 mg·kg⁻¹对小鼠灌胃给药, 采集给药后不同时间点血浆样本, 用HPLC检测血浆药物浓度, 分析平均血药浓度经时变化并计算药动学参数。以小鼠自主活动计数为药效学指标, 观测MOD 120 mg·kg⁻¹灌胃给药后不同时间段内小鼠自主活动量 (计数) 的变化, 分析与血浆药物浓度变化的相关性。结果显示, MOD在小鼠体内药动学过程符合二室模型, t_1/2α, t_1/2β, t_max, C_max, AUC_0−∞分别为0.42 h, 3.10 h, 1.00 h, 41.34 mg·L⁻¹和142.22 mg·L⁻¹·h。MOD使小鼠自主活动明显增多, 持续约4 h, 且与血浆药物浓度呈同步变化, 二者间存在明显的相关性。     

Pharmacokinetics,tissue distribution and safety of cinnarizine delivered in lipid emulsion

The aim of this study was to assess the potential of cinnarizine loaded in lipid emulsion to modify the pharmacokinetics, tissue distribution and safety of cinnarizine. The cinnarizine-loaded emulsion (CLE) which can remain stable over 18-month storage at 4 ± 2 °C was prepared by high-pressure homogenization. Nicomp? 380 particle sizing system and HPLC were used to evaluate CLE in vitro, while UPLC/MS/MS for pharmacokinetic and tissue distribution study. The pharmacokinetics and tissue distributions of CLE were assessed by comparing with the solution form after intravenous administration to rats at a dose of 2 mg/kg. The CLE showed significant higher AUC and lower clearance and distribution volume than those of solution form. This helped cinnarizine to reach higher level in vessel, and circulate in the blood stream for a longer time resulting in better therapeutic effect. The tissue distribution exhibited significant lower uptake of CLE emulsion in lung and brain, indicating the advantage of CLE over the solution form in reducing drug precipitation in vivo and toxicity in CNS. Drug safety assessment studies including hemolysis test, intravenous stimulation and injection anaphylaxis revealed that the CLE was safe for intravenous injection.     

注射用克拉霉素乳剂的制备及其体内外评价

目的制备克拉霉素乳剂并考察其刺激性和体内药物动力学行为。方法通过高压均质方法制备克拉霉素乳剂，并对其性质进行研究。以克拉霉素溶液剂为对照，观察了乳剂的刺激性和在大鼠体内的药物动力学行为。结果高压均质法制备克拉霉素乳剂，平均粒径为156 nm，zeta 电位为-31.8 mV。于4 ℃留样观察6个月内样品稳定。与克拉霉素溶液剂相比，乳剂可以明显降低刺激性。两种制剂在大鼠体内的药物动力学曲线相似，符合双隔室模型。克拉霉素乳剂和溶液剂AUC0-t分别为(66.76±16.34)和(59.00±11.20) μg·h·mL^-1。结论高压均质法可以制备出性质稳定的载药乳剂，克拉霉素乳剂可以明显降低静脉注射时引起的刺激性。     

Metabolic fate of diltiazem. Distribution, excretion and protein binding in rat and dog

Pharmacokinetics of (+)-(2S,3S)-2,3-dihydro-3-acetoxy-2-(4-methoxyphenyl)-5- [2-(dimethylamino)ethyl]-1,5-benzothiazepin-4(5H)-one hydrochloride (diltiazem-HCl, Cardizem, Herbesser) in rats and dogs were investigated using 14C-diltiazem-HCL. The plasma concentration of unchanged drug in rats was 1.78 microgram/ml 1 min after intravenous administration at a dose of 3 mg/kg, and rapidly decreased thereafter with a half-life of 20 min (alpha-phase) and 56 min (beta-phase). In contrast, the plasma concentration of radioactivity in rats increased during 0-2 h in spite of intravenous administration, and thereafter the level of radioactivity in plasma decreased very slow. In dogs, the plasma concentration of unchanged drug was 0.138 micrograms/ml 1 min after intravenous administration at a dose of 0.2 mg/kg, and then decreased with a half-life of 2.5 min (alpha-phase) and 1.68 h (beta-phase). Dog plasma level of radioactivity decreased once after intravenous administration, but increased from 30 min to 1 h. Unchanged drug plasma levels at 1 h after intravenous administration were 6.6 and 35.1% of the plasma radioactivities in rats and dogs, respectively. When 14C-diltiazem-HCl was orally administered, unchanged drug plasma levels in rats and dogs were 1.8 and 12.8% of the plasma radioactivities at 15 min, respectively. Therefore, the first-pass effect was extensive, especially in rats. Rat whole body autoradiograms showed that radioactivity distributed well to tissues and organs in either route of administration. Similar results were obtained by the method of counting the radioactivity in the tissues and organs of rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacokinetics of the new pyrimidine derivative NS-7, a novel Na+/Ca2+ channel blocker. 2nd communication: tissue distributions, placental transfer and milk secretion of radioactivity after a single intravenous 14C-NS-7 injection to rats

Tissue distribution, placental transfer and secretion of radioactivity in milk were studied after a single intravenous administration of 0.2 mg/kg of 14C-NS-7 (4-(fluorophenyl)-2-methyl-6-(5-piperidinopentyloxy)pyrimidine hydrochloride, CAS 178429-67-9), a novel Na+/Ca2+ channel blocker, to rats. Except for white fat in male and female rats, tissue radioactivity concentrations 5 min after administration were 2 to 100 times the plasma values, evidence that the drug is widely distributed throughout the body. Five minutes after administration the highest concentration was in the lung followed in order by the adrenal gland, kidney and thyroid gland. Concentrations in the cerebral cortex, striatum and cerebellum, the target organs of NS-7, were similar and 10 to 18 times the plasma concentrations in the male and female rats. Radioactivity concentrations in the lungs decreased rapidly. The pancreas had the highest concentration 2 h after administration. Concentrations decreased in all the tissues examined as the plasma concentration decreased. Maternal and fetal tissue radioactivity concentrations were determined after intravenous injection of 14C-NS-7 to pregnant rats on the 18th day of gestation. Radioactivity was well and rapidly distributed to the maternal tissues, and concentrations in all the tissues tested were higher than the plasma concentrations. In the amniotic fluid, however, the concentration was lower than in the plasma. In all the fetal tissues tested, radioactivity reached a maximum 1 h after administration. The respective fetal blood and whole body concentrations were 2 to 6 and 11 to 13 times the maternal plasma concentration. Of the fetal tissues tested the liver had the highest radioactivity. Decreases in fetal tissue radioactivity concentrations paralleled the decrease in the maternal plasma. More than 90% of the radioactivity present in the placenta and fetal whole body 1 and 24 h after administration was due to the unchanged drug. After intravenous injection of 14C-NS-7 (0.2 mg/kg) to lactating rats on the 10-14th day after parturition, radioactivity was excreted rapidly into the milk, reaching a maximum that was 4 to 6 times the plasma value 1 h after injection.     

Evaluation of the pharmacokinetics of all-trans-retinoic acid (ATRA) in Wistar rats after intravenous administration of ATRA loaded into tributyrin submicron emulsion and its cellular activity on caco-2 and HepG2 cell lines

The pharmacokinetics of all-trans-retinoic acid (ATRA), an anti-cancer drug was highly variable due to its poor aqueous solubility. In this study, we investigated the pharmacokinetics of ATRA in male Wistar rats following intravenous administration of the ATRA loaded tributyrin emulsion. In vitro, the ATRA emulsion was proved binding to apolipoprotein(s). In vivo, the clearance of ATRA was significantly reduced by formulating into the tributyrin emulsion, leading to higher AUCs. Co-administration with 17alpha-ethynylestradiol, a compound known to upregulate the activity of low-density lipoprotein receptors in tissues, significantly increased the K(e), V, and CL of ATRA. The variation of plasma AUCs after administering the ATRA emulsion to the healthy rats was two times less than that after the ATRA solution. The IC(50) in ATRA of the ATRA emulsion for the Caco-2 carcinoma cells was 3.8 microg/mL lower than 6 microg/mL of the ATRA solution. The IC(50) of the emulsion for the HepG2 carcinoma cells was 2.8 microg/mL, while IC(50) was not achieved with the ATRA solution over the test concentration range. The finding indicated that the tributyrin emulsion could be used as a carrier for ATRA and enhances the drug effect by reducing the clearance and increasing the in vitro activity.     

3＇单肟靛玉红的药物代谢动力学研究

目的研究3＇单肟靛玉红（IMX）在大鼠体内的药物代谢动力学过程。方法利用高效液相色谱法（HPLC）测定大鼠血液中IMX的含量;分别研究静脉注射、腹腔注射2种给药途径后,IMX在大鼠体内的药物代谢动力学,应用3P87药物代谢动力学程序,计算出主要的药物代谢动力学参数;并进一步观察静脉给药后药物在动物体内主要器官心、肺、肾、脑组织中IMX的含量。结果鼠尾静脉注射IMX,药物代谢动力学符合二室模型。IMX在鼠体内吸收快、分布快、药物起效快,在体内主要以消除过程为主,药物在体内滞留时间较长。静脉注射10 mg/kg IMX,于不同时间处死,用HPLC测定各组织中IMX的含量,结果发现,IMX在心脏组织中含量较高,在1 h达峰值;脑组织、肺组织中IMX含量在0.5 h即达峰值;肾脏组织中IMX含量在3 h达峰值。IMX主要分布在体循环和血流丰富的脏器中。结论应用HPLC法测定大鼠血浆中IMX的浓度,操作简便、省时,精密度及重现性均较好。静脉注射IMX,药物代谢动力学符合二室模型,IMX在鼠血中主要以消除过程为主,IMX主要分布在血流丰富的组织中,分布速率较快。IMX易于透过血脑脊液屏障。     

In vivo studies on the oridonin-loaded nanostructured lipid carriers

Oridonin (ORI)-loaded Nanostructured lipid carriers (NLC) were prepared by emulsion–evaporation and low temperature–solidification technique, and evaluated for morphological observation, particle size, zeta potential and in vitro drug release. Next, the characteristics of biodistribution and pharmacokinetics in vivo were examined. The average particle size of resultant NLC was 245.2?nm and the zeta potential was found to be -38.77 mV. The in vivo characteristics of ORI-loaded NLC were studied after intravenous administration using Kunming strain mice as experimental animals. An ORI control solution was studied parallelly. In tested organs, the distribution of ORI-loaded NLC to liver was higher than that of free drug. ORI-loaded NLC showed higher AUC (area under tissue concentration–time curve) values and circulated in the blood stream for a longer time compared with ORI solution. These results support the potential applications of NLC for the delivery of ORI.     

Pharmacokinetics of falintolol II. Absorption, distribution and elimination from tissues and organs following ocular administration and intravenous injection of falintolol in albino rabbits

The absorption, distribution and elimination of falintolol maleate was studied in various ocular and extraocular tissues and organs following ocular instillation, intravenous injection of a 0.5% 14C-falintolol ophthalmic solution and repeated ocular instillations of a 1% non-labeled falintolol ophthalmic solution into albino New Zealand rabbits. Falintolol was distributed in all studied tissues and organs after both routes of administration. After ocular instillation, levels of total radioactivity were distinctly higher in ocular tissues than after intravenous injection. Thus, the level was 475 times more important in cornea, 72 times in aqueous humor and 36 times in iris and ciliary body after ocular instillation. On the other hand, levels of total radioactivity in extraocular tissues and organs were 30-50% higher after intravenous injection compared to ocular instillation of the same dose. Peak levels of total radioactivity were generally achieved between 30 min and 1 h after ocular instillation, while 1.5 h after intravenous injection an increase in the declining part of the curve occurred. This increase, characteristic of an enterohepatic reabsorption, was also observed in blood and plasma 1 h after intravenous injection. Urinary elimination was the major means of excretion since 79.6% of total radioactivity was found in urine 6 h after intravenous injection and 74.5% 12 h after ocular instillation. But after ocular instillation, only 5% was excreted as unchanged falintolol. Whatever the route of administration, after single or repeated application, no drug accumulation was evident.     

Pharmacokinetics of 4-acetylaminophenylacetic acid. 1st communication: absorption, distribution, metabolism and excretion in mice, rats, dogs and monkeys after single administration of 14C-labeled compound

Absorption, distribution, metabolism and excretion of 4-acetylaminophenylacetic acid (MS-932) were studied in mice, rats, dogs and monkeys after intravenous or oral administration of 5 or 10 mg/kg of 14C-MS-932. After the intravenous injection of 14C-MS-932, the radioactivity concentrations in the plasma decreased biexponentially. The half-lives of the elimination phase (t1/2, beta) were 2.58 h for mice, 2.35 h for rats, 1.88 h for dogs and 1.24 h for monkeys. After the oral administration of 14C-MS-932, the radioactivity concentrations in the plasma reached maximums between 0.4 and 1.3 h, thereafter decreasing with half-lives similar to those found for the intravenous injection. The systemic availability of this drug was 72-100% in all the species tested. No clear sex-related difference in radioactivity concentrations was found in rat plasma. After both intravenous and oral administrations, in all the species tested, almost all the radioactivity administered was excreted in the urine. Biliary excretion of radioactivity in bile duct-cannulated rats was only 1.42% of the intravenous dose over a 24-h period. Lymphatic absorption of radioactivity was negligible (0.2% of the dose over a 6-h period). After oral administration of 14C-MS-932, the radioactivity concentrations in the rat tissues tested reached maximums within 1 h, decreasing rapidly thereafter similar to the decrease in the concentration in the plasma. Much higher concentrations were present in the kidney and gastro-intestinal tract than in the plasma, whereas the concentrations in the other tissues were lower. Results obtained by whole-body autoradiography were consistent with those obtained for the radioactivity in excised tissues.(ABSTRACT TRUNCATED AT 250 WORDS)