Tissue distribution of cadmium and its effect on reproduction in Spodoptera exigua

Vegetable fields are often contaminated by heavy metals,and Spodoptera exigua is a major vegetable pest which is stressed by heavy metals mainly by feeding.In this study,cadmium accumulation in the tissues of S.exigua exposed to cadmium and its effects on the growth and development of the parents and the offspring were investigated.Under the stress of different concentrations of cadmium(0.2,3.2,and 51.2 mg kg^(-1)),the cadmium content in each tissue of S.exigua increased in a dose-dependent manner.At the larval stage,the highest cadmium accumulation was found in midgut in all three cadmium treatments,but at the adult stage,the highest cadmium content was found in fat body.In addition,the cadmium content in ovaries was much higher than in testes.When F1S.exigua was stressed by cadmium and the F_(2)generation was not fed a cadmium-containing diet,the larval survival,pupation rate,emergence rate and fecundity of the F_(2)generation were significantly reduced in the 51.2 mg kg^(-1)treatment compared to the corresponding F1generation.Even in the F_(2)generation of the 3.2 mg kg^(-1)treatment,the fecundity was significantly lower than in the parental generation.The fecundity of the only-female stressed treatment was significantly lower than that of the only-male stressed treatment at the 3.2 and 51.2 mg kg^(-1)cadmium exposure levels.When only mothers were stressed at the larval stage,the fecundity of the F_(2)generation was significantly lower than that of the F1generation in the 51.2 mg kg^(-1)treatment,and it was also significantly lower than in the 3.2 and 0.2 mg kg^(-1)treatments.The results of our study can provide useful information for forecasting the population increase trends under different heavy metal stress conditions and for the reliable environmental risk assessment of heavy metal pollution.

Development and Validation of UHPLC-MS/MS Method for Quantifying of Agarotriose:An Application for Pharmacokinetic,Tissue Distribution,and Excretion Studies in Rats

A sensitive,rapid,and robust ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS)method was established for the first time to quantify agarotriose(A3)in rat plasma,tissues,urine,and feces.A3 and stachyose(internal standard)were separated by a BEH amide column at 65℃under the mobile phase of 10 mmol L^(-1)ammonium ace-tate-acetonitrile(42:58,v/v)with 350µLmin-1.The acquisition of transitions was carried out in multiple reaction monitoring(MRM)pattern operating with positive ionization at m/z 509.16>329.15 for A3 and m/z 689.15>527.11 for stachyose.The linearity ranges of A3 were 10 to 5000nmolL^(-1)for plasma,20 to 10000nmolL^(-1)for tissues,and 40 to 20000nmolL^(-1)for urine and feces.The accuracy and precision ranged from 90.9%to 111.6%and 0.7%to 10.1%,respectively.The stability was between 86.1%and 102.5%.The extraction recovery was consistent and reproducible.The matrix effect ranged from 1.5%to 11.4%.The pharmacokinetic,tissue dis-tribution,and excretion studies were successfully conducted with the validated method.Results showed that A3 could be absorbed by rats,and the absolute bioavailability was 6.7%.Furthermore,it was rapidly distributed in rat tissues and mainly eliminated via feces excretion(67.0%)after oral administration.For intravenous bolus,85.5%was recovered,and renal excretion was the primary path-way(77.6%)for cumulative recovery.

Tissue distribution,excretion and pharmacokinetics of R-hap in rats

The purpose of this study is to characterize the tissue distribution, excretion and pharmacokinetics profiles of R-hap in healthy Wistar rats. R-hap was radiolabeled by the IODO-GEN method. Tissue distribution and urinary, fecal and biliary excretion patterns of ^125I-R-hap were investigated following a single i.v. bolus injection. Pharmacokinetics properties of ^125I-R-hap were also examined after a single i.v. bolus injection. The trichloroacetic acid （TCA） precipitated radioactivity was widely distributed and rapiclly diminished in most tissues. Kidney contained the highest radioactivity among all organs and the distribution of ^125I-R-hap to fat was minimal. The cumulative excretion of ^125I-R-hap reached 71.81% ± 2.15% of the administered radioactivity at 48 h and 94.71% ± 1.50% at 120 h. Urinary excretion was the dominant route of elimination following i.v. administration, as 80.64% ± 1.47% and 14.07% ± 0.95% of administered radioactivity were recovered in urine and feces, respectively, in intact rats over 120 h. The mean areas under the plasma concentration-time curve was （8818.4 ± 576.1） Bq/h/mL. The results of tissue distribution, excretion and pharmacokinetics of R-hap in rats provided biopharmaceutical basis for the design of future clinical trials.

Pharmacokinetics and tissue distribution of intraperitoneal 5-fluorouracil with a novel carrier solution in rats

AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution with middle molecular weight and physiologic saline (0.9% sodium chloride solution), a traditional carrier solution for intraperitoneal chemotherapy, in rats. METHODS: A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Each group was further randomized according to the intraperitoneal dwell period (1, 3, 6, 12, 18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and quantitated. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high- performance liquid chromatography. RESULTS: The mean volumes remaining in the peritoneal cavity were significantly higher with HAES- steri than those with physiologic saline at 1, 6, 12, 18, and 24 h (P = 0.047, 0.009, 0.005, 0.005 and 0.005 respectively, the percentages of remaining peritoneal fluid volume were 89.9 ± 5.6 vs 83.4 ± 4.9, 79.9 ± 2.8 vs 56.2 ± 15.7, 46.8 ± 5.5 vs 24.7 ± 9.7, 23.0 ± 2.8 vs 0.0 ± 0.0 and 4.2 ± 1.7 vs 0.0 ± 0.0 respectively). Mean concentrations in peritoneal fluid were significantly higher with HAES-steri than those with physiologic saline at 3, 12 and 18 h (P = 0.009, 0.009 and 0.005 respectively, the concentrations were 139.2768 ± 28.2317 mg/L vs mg/L, 11.5427 ± 3.0976 mg/L vs 0.0000 ± 0.0000 mg/L and 4.7724 ± 1.0936 mg/L vs 0.0000 ± 0.0000 mg/L respectively). Mean plasma 5-fluorouracil concentrations in portal vein were significantly higher with HAES-steri at 3, 12, 18 and 24 h (P = 0.009, 0.034, 0.005 and 0.019 respectively, the concentrations were 3.3572 ± 0.8128 mg/L vs 0.8794 ± 0.2394 mg/L, 0.6203 ± 0.9935 mg/L vs 0.0112 ± 0.0250 mg/L, 0.3725 ± 0.3871 mg/L vs 0.0000 ± 0.0000 mg/L, and 0.2469 ± 0.1457 mg/L vs 0.0000 ± 0.0000 mg/L respectively), but significantly lower at 1 h (P = 0.009, the concentrations were 4.1957 ± 0.6952 mg/L vs 7.7406 ± 1.2377 mg/L). There were no significant differences in the plasma 5-fluorouracil in inferior caval vein at each time-point. 5-fluorouracil concentrations were significantly greater with HAES-steri at 18 h in gastric tissue (P = 0.016, the concentrations were 0.9486 ± 0.8173 mg/L vs 030392 ± 0.0316 mg/L), at 18 h in colon (P = 0.009, the concentrations were 0.1730 ± 0.0446 mg/L vs 0.0626 ± 0.0425 mg/L), at 3, 6, 12 and 24 h in liver (P = 0.009, 0.013, 0.034 and 0.013 respectively, the concentrations were 0.6472685 ± 0.5256 mg/L vs 0.1554 ± 0.1043mg/L, 0.8606826 ± 0.7155 mg/L vs 0.0014 ± 0.0029 mg/L, 0.0445 ± 0.0330 mg/L vs 0.0797 ± 0.1005 mg/L and 0.0863 ± 0.0399 mg/L vs 0.0034 ± 0.0075 mg/L respectively) and at 18 h in lung (P = 0.009, the concentrations were 0.0886 ± 0.0668 mg/L vs 0.0094 ± 0.0210 mg/L). There were no differences in 5-fluorouracil concentrations in renal tissue at each time-point. CONCLUSION: The use of intraperitoneal 5-fluoro- uracil with HAES-Steri carrier solution provides a pharmacokinetic advantage for a local-regional killing of residual tumor cells and improve the accumulated penetrability of 5-fluorouracil with decreased systemic toxicity. Further clinical feasibility studies on the use of HAES-steri as carrier solution for intraperitoneal chemotherapy with 5-fluorouracil are warranted.

Absolute bioavailability,dose proportionality,and tissue distribution of rotundic acid in rats based on validated LC-QqQ-MS/MS method

Rotundic acid(RA),an ursane-type pentacyclic triterpene acid isolated from the dried barks of Ilex rotunda Thunb.(Aquifoliaceae),possesses diverse bioactivities.To further study its pharmacokinetics,a simple and sensitive liquid chromatography with triple quadrupole mass spectrometry(LC-QqQ-MS/MS)method was developed and validated to quantify RA concentration in rat plasma and tissue using etofesalamide as an internal standard(IS).Plasma and tissue samples were subjected to one-step protein precipitation.Chromatographic separation was achieved on a ZORBAX Eclipse XDB-C_(18) column(4.6mm×50mm,5μm)under gradient conditions with eluents of methanol:acetonitrile(1:1,V/V)and 5mM ammonium formate:methanol(9:1,V/V)at 0.5mL/min.Multiple reaction monitoring transitions were performed at m/z 487.30→437.30 for RA and m/z 256.10→227.10 for IS in the negative mode.The developed LC-QqQ-MS/MS method exhibited good linearity(2-500 ng/mL)and was fully validated in accordance with U.S.Food and Drug Administration bioanalytical guidelines.Dose proportionality and bioavailability in rats were determined by comparing pharmacokinetic data after single oral(10,20,and 40mg/kg)and intravenous(10mg/kg)administration of RA.Tissue distribution was studied following oral administration at 20mg/kg.The results showed that the absolute bioavailability of RA after administration at different doses ranged from 16.1%to 19.4%.RA showed good dose proportionality over a dose range of 10-40 mg/kg.RA was rapidly absorbed in a dose-dependent manner and highly distributed in the liver.In conclusion,this study is the first to systematically elucidate the absorption and distribution characteristics of RA in rats,which can provide additional information for further development and evaluation of RA in drug metabolism and pharmacokinetic studies.

Tissue Distribution of [^3H]—Nicotine in Rats

This study was conducted in adult male Sprague -- Dawley rats to determine the distribution of [3H]-nicotine in blood and tissues following a bolus injection and a constant infusion of pure nicotine. The animals were anesthetized and injected with either 0.5 ml of nicotine solution or given a constant infusion of the same nicotine solution with identical amounts of radioactive nicotine. After sacrifice, blood, brain, trachea, salivery gland, esophagus, lung, heart, liver, fundus, antrum, spleen, pancreas, duodenum, jejunum, ileum, cecum, colon, kidneys, adrenal gland, and testes were collected and measured for radioactivity by scintillation counting. The distribution of nicotine was found highest in kidneys by both routes of administration. Higher accumulations were also found in salivary and adrenal glands, fundus, antrum, duodenum, jejunum, ileum and colon. Retention of nicotine via constant infusion was significantly higher in esophagus, fundus antrum, spleen, cecum, pancreas, testes, heart and muscle when compared with bolus injection. Six-fold increase in retention of blood levels of nicotine were found with constant infusion. (P<0.05). The results indicate that longer retention of nicotine occurs in blood and other specific tissues such as esophagus, fundus, antrum, spleen, cecum, pancreas, testes, heart and muscle via constant exposure. These data may implicate the predisposition of these tissues to pathologic manifestations.

Pharmacokinetics and Tissue Distribution of Clevidipine and Its Metabolite in Dogs and Rats

The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H 152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/（kg·min）, and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short （16.8 min）, pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/（min·kg）. In comparison, plasma concentra- tion of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the high- est concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small （0.042‰） compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite raoidlv.

Herb-drug interaction in the protective effect of Alpinia officinarum against gastric injury induced by indomethacin based on pharmacokinetic, tissue distribution and excretion studies in rats

Alpinia officinarum Hance of the Chinese traditional herb for the treatment of emesis, abdominal pain and diarrhea has been used to counteract gastric disease induced by indomethacin in rats without obvious side effects. However, the role of herb-drug interaction between indomethacin and A. officinarum based on pharmacokinetic, tissue distribution and excretion still remains unknown. In this study, an ultra-fast liquid-tandem mass spectrometry(UFLC-MS/MS) method was developed for simultaneous determination of indomethacin and its three metabolites, O-desmethylindomethacin(ODI), deschlorobenzoylindomethacin(NDI) and indomethacin acyl-b-D-glucuronide(IDAbG) by oral administration of indomethacin solution with and without the ethanolic extract of A. officinarum and applied to comparative pharmacokinetic, tissue distribution and excretion studies. Our results clarified that oral administration of A. officinarum produced significant alterations in the pharmacokinetic parameters of indomethacin. And the pharmacokinetic interaction between indomethacin and A. officinarum reduced the systemic exposure of indomethacin and increased its elimination. Tissue distribution results demonstrated that co-administration of A. Officinarum could not reduce the accumulation of indomethacin in the target tissue of the stomach, but could accelerate the excretions of indomethacin and its three metabolites including ODI, NDI and IDAb G in the bile and feces of rats in the excretion study.Therefore, A. Officinarum might have a gastrointestinal protective effect through the interaction role with indomethacin based on the pharmacokinetics and excretion in rats.

Tissue distribution of deoxynivalenol in piglets following intravenous administration

Contamination of deoxynivalenol（DON） in grains is common worldwide and pigs are particularly susceptible to this mycotoxin. The distribution of DON in porcine tissues following intravenous administration was investigated in this study. Fifteen pigs were randomly divided into three groups. Animals in groups A and B were administrated with DON at the dose of 250 and 750 μg kg–1 body weight, respectively, while group C served as blank control. Plasma, bile and 27 tissues were collected at 30 min post-administration. DON concentrations in all samples were tested using high-performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS）. To observe the distribution of DON in tissues, these samples were further subjected to the immunohistochemical analyses. Totally, the bile and 13 tissues were sampled for DON-based detection, including kidney, mesenteric lymph nodes, muscle, stomach, jejunum, colon, plasma, spleen, rectum, cecum, liver, ileum, and duodenum. No significant difference was observed for the concentrations of DON in duodenum, ileum and liver samples between groups A and B; while the DON concentrations in cecum and rectum of group B were significantly higher（P-value 〈0.05） than those in group A. In addition, the DON concentrations in stomach, jejunum, colon, mesenteric lymph nodes, muscle, kidney, spleen, bile, and plasma of group B were remarkably higher than those of group A（P-value〈0.01）. Levels of DON in other 14 tissues including medulla oblongata, midbrain, diencephalon, pons, tip and tongue body, tongue, soft palate, tonsils, pharyngeal mucosa, oral buccal mucosa, thymus, thyroid, esophagus and adrenal gland were all below the limit of detection. The results of immunohistochemistry showed that 11 tissue samples（medullaoblongata, tonsil, adrenal medulla, thyroid gland, thyroid, stomach, duodenum, jejunum, kidney, spleen, and mesenteric lymph nodes） were positive and DON was mainly distributed around blood vessels in these tissues. Therefore, we believed that concentrations of DON in tissues differ when pigs are in exposure to various dosages and DON causes lesions in many pig tissues.

Disposition and Tissue Distribution of ML12 in Rats

To investigate the disposition and tissue distribution of ML12 after intravenous （iv） administration in rats, the compound in plasma or in tissue was extracted into ethyl acetate under basic condition and was determined by HPLC after extracted by dilute sulfuric acid. Excitation wavelength and emission wavelength of fluorescence detection were 278 nm and 307 nm, respectively. The data were processed with the software 3P97 to calculate the main pharmaceutical parameters of ML12. At dose of 5 and 10 mg/kg, the elimination of the drug from plasma was found to be kinetically linear, but when the dosage was 20 mg/kg, a non-linear feature was observed. The highest level of ML12 was found in the kidney. Distribution of ML12 after iv administration was extensive and the concentration-time profile was found to be fitted to an open two-compartment model.

Pharmacokinetic Study and Tissue Distribution of Single Mangiferin After Intravenous Administration in Rats

A simple, sensitive ane selective high performance liquid chromatographic （HPLC） method with UV detection （320 nm） was developed and validated for determination of mangiferin in rat plasma and tissues. Mangiferin and internal standard （spinosin） were separated using mobile phase of acetonitrile-water （20：80, v/v） with 1% glacial acetic acid and 1% THF on a Phenomenex gemini C18 column. The flow rate was 0.7 mL/min. The calibration curves of mangiferin in plasma and tissues were linear over the investigated ranges. The intra- and inter-run preeisions for all samples were less than 13.8 %. The time-concentration curve of mangiferin after intravenous administration to rats corresponded to two-compartment model. The main pharmacokinetic parameters T0.5α, T0.5β, CL and AUC0-T were 15.87 min, 26.15 rain, 6.1 L/（min·kg） and 3.28 mg· min/mL, respectively. The highest and lowest levels of mangiferin occurred in spleen and brain, respectively. Mangiferin was not found in liver. After intravenous administration, the drug was distributed extensively and transferred quickly in rats in vivo.

Diazinon Toxicokinetics, Tissue Distribution and Anticholinesterase Activity in the Rat

The toxicokinetics, tissue distribution, and anticholinesteruse (antiChE ) activity of diazinon were investigated in the rat. Plasma concentrations most adequately fitted a two-compartment open model after iv administration of 10 mg/kg and a one-compartment model after oral administration of 80 mg/kg. Diazinon elimination half-life following iv and oral dosing was 4.70 and 2.86 h, respectively. The oral bioavailabllity was found to be low (35.5%). Hepatic extraction ratios after iv administration of 5 or 10 mg

Tissue distribution of Lycium barbarum polysaccharides in rat tissue by fluorescein isothiocyanate labeling

To date, in vivo investigations of polysaccharide’s pharmacokinetics are significantly restricted by the difficulty in their detection. This study was conducted to establish the quantitative determination of Lycium barbarum polysaccharides(LBPs) based on fluorescein isothiocyanate(FITC) pre-labeling and to investigate their tissue distribution in rat. We obtained the calibration curves linear over the range of 0.0–25 μg/m L in rat tissue samples with correlation coefficients greater than 0.99. The inter-day and intra-day precisions(RSD, %) were within 15%, and the relative recovery ranged 95.2%–102.4%, with RSD range 1.48%–9.58%, indicating that this experiment was suitable for the determination of LBPs. The fluorescence intensity was measured after 24 h storage at room temperature, 3 times of freeze-cycle and cryopreservation at –20 ℃ for 15 day, these results indicated that the stability of the samples was good. LBP-FITC was mainly absorbed by the small intestine and stomach, and mainly excreted in the urine through the kidney;this distinct difference in the tissue distribution of LBPs could be attributed to the size of these LBPs in relation to the pore sizes of the vascular beds in the kidney and liver. Results showed in this study enable us to comprehensively understand the biological effects of LBPs following its oral ingestion.

Determination of 6258-70,a new semi-synthetic taxane,in rat plasma and tissues:Application to the pharmacokinetics and tissue distribution study

Cancer is the leading cause of death all over the world.Among the chemotherapy drugs,taxanes play an important role in cancer treatment.6258-70 is a new semi-synthetic taxane which has a broad spectrum of antitumor activity.A fast and reliable high performance liquid chromatography-tandem mass spectrometry（HPLC-MS/MS） method was developed for quantification of 6258-70 in rat plasma and tissues in this paper.After extraction by liquid-liquid extraction method with methyl tert-butyl ether,the samples were separated on a Kinetex C_（18） column（50 mm × 2.1 mm,2.6 μm,Phenomenex,USA） within3 min.The method was fully validated with the matrix effect between 87.7%and 99.5%and the recovery ranging from 80.3%to 90.1%.The intra- and inter-day precisions were less than 9.5%and the accuracy ranged from-3.8%to 6.5%.The reliable method was successfully applied to the pharmacokinetics and tissue distribution studies of 6258-70 after intravenous administration in rats.The pharmacokinetic results indicated that the pharmacokinetic behavior of 6258-70 in rats was in accordance with linear features within tested dosage of 1 to 4 mg/kg,and there was no significant difference between the two genders.The tissue distribution study showed that 6258-70 had an effective penetration,spread widely and rapidly and could cross blood-brain barrier.The results of pharmacokinetics and tissue distribution may provide a guide for future study.

Influence of Exposure Pathways on Tissue Distribution and Health Impact of Polycyclic Aromatic Hydrocarbon Derivatives

The oxygen(OPAHs),nitro(NPAHs),hydroxyl(OH-PAHs),and alkylated(APAHs)derivatives of polycyclic aromatic hydrocarbon(PAHs)are ubiquitous pollutants in the environment.The concentrations of NPAHs,OPAHs,OH-PAHs,and APAHs are lower than that of PAHs in the environment,but the carcinogenic abilities of the derivatives are usually 10 to 1,000-fold higher than that of parent PAHs.There are three main pathways for the exposure of polycyclic aromatic compounds to humans,including inhalation,direct contact,and ingestion.After exposure by inhalation,they are mainly distributed in the lungs,affecting lung function and causing inflammation,asthma,etc.Due to the digestive system’s strong capacity for metabolism,intake of PAHs and the derivatives is primarily distributed in the digestive system and metabolized there.And it may lead to dysplasia of these organs and even to cancer.The skin is the primary site of direct contact with PAH derivatives.PAH derivatives can enter the bloodstream through all three contact pathways,thereby accumulating in various organs.This study aimed to summarize the influence of exposure pathways on tissue distribution and the health impact of PAH derivatives to provide references for future research and evaluation on public health.

The Uptake and Distribution Evidence of Nano-and Microplastics in vivo after a Single High Dose of Oral Exposure

Objective Tissue uptake and distribution of nano-/microplastics was studied at a single high dose by gavage in vivo.Methods Fluorescent microspheres(100 nm,3μm,and 10μm)were given once at a dose of 200 mg/(kg∙body weight).The fluorescence intensity(FI)in observed organs was measured using the IVIS Spectrum at 0.5,1,2,and 4 h after administration.Histopathology was performed to corroborate these findings.Results In the 100 nm group,the FI of the stomach and small intestine were highest at 0.5 h,and the FI of the large intestine,excrement,lung,kidney,liver,and skeletal muscles were highest at 4 h compared with the control group(P<0.05).In the 3μm group,the FI only increased in the lung at 2 h(P<0.05).In the 10μm group,the FI increased in the large intestine and excrement at 2 h,and in the kidney at 4 h(P<0.05).The presence of nano-/microplastics in tissues was further verified by histopathology.The peak time of nanoplastic absorption in blood was confirmed.Conclusion Nanoplastics translocated rapidly to observed organs/tissues through blood circulation;however,only small amounts of MPs could penetrate the organs.

Study on pharmacokinetic and tissue distribution ofisovitexin in rats by HPLC

An HPLC method for the determination of isovitexin in rat plasma and different tissues was developed.The separation was achieved on a C_（18）column with a mobile phase consisting of methanol-1% acetum（40：60,v/v）at a detection wavelength of 338 nm and a column temperature of 30℃.Rutin was chosen as the internal standard.The linear range of the standard curves was 0.20-128.75μg/mL in the plasma and 0.024-3.09μg/mL in the tissues.The LOQ was 0.19μg/mL in the plasma and 0.024μg/mL in the tissues.The relative recoveries of isovitexin ranged from 93% to 105% in the plasma and 87% to 112% in the tissues.The intra-and inter-day precisions were all below 8%.The pharmacokinetics and tissue distribution of isovitexin in rats were studied with the method.Blood samples were collected at fixed time intervals after the i.v.injection of isovitexin at a dosage of 18.75,3.75 and 0.75 mg/kg;the tissue samples（brain,liver,kidney,heart,lung,spleen and ovary）were obtained at 10,30,and 60 min after the i.v.injection of isovitexin at a dosage of 18.75 mg/kg.The pharmacokinetics of the isovitexin in three different dosages in the rats fit the two-compartment open model.The isovitexin displayed linear dynamics in the dosage range of 0.75-18.75 mg/kg.The mean value of t_（1/2α）was 1.54-1.84 min,and t_（1/2β）was 36.94-46.27 min at the three dosages.The tissue distribution study showed that the sequence of tissue drug concentration from high to low was kidneyliverlung≈ovaryheart≈spleenbrain.

Preparation of lomustine loaded liposomes and studies of its pharmacokinetics and tissue distribution properties

Liposomes are used as carriers for targeted drug delivery by the intravenous route. The aim of our study was to prepare lomustine loaded liposomes （CCNU-Lips） and evaluate its physicochemical properties and the tissue targeting after intravenous （i.v.） injection. CCNU-Lips were prepared by film dispersion method. In vitro drug release was investigated in phosphate-buffered saline （pH 6.8） at 37℃. The concentrations of CCNU in selected organs were determined using reversed-phase high-performance liquid chromatography （HPLC） following i.v. administration of CCNU-Lips and inclusion complex solution of CCNU with hydroxypropyl-β-cyclodextrin （CCNU-Sol）. CCNU-Lips had an average diameter of （189.8±28.5） nm with a zeta potential of （-19.13±0.12） mV and the in vitro drug release was monitored for up to 3 d, and the release behavior was in accordance with Weibull-equation. The CCNU-Lips exhibited a longer elimination half life （t1/2β） in vivo compared with CCNU-Sol after i.v. injection to New Zealand rabbits. The encapsulation of lomustine in liposomes also changed its biodistribution in mice. CCNU-Lips showed significant brain targeting with AUC, Te and Re of the brain all showing obvious elevation. These results indicated that CCNU-Lips were promising passive targeting formulation to the brain.

Studies on tissue distribution and excretion of scopoletin after oral administration in rats

The present study aimed at studying the characteristics of tissue distribution and excretion of scopoletin,a coumarin compound,in Sprague-Dawley rats.Scopoletin was orally administered at a dose of 50 mg/kg,and the concentrations in heart,liver,spleen,lung,kidney,muscle,fat,brain,testis,uterus,stomach and small intestine were determined at 5,15,30,60,120,240 min post-dose,respectively.It was shown that scopoletin was widely distributed into various tissues and reached the maximal concentrations in most tissues at 15 min post-dose,and the levels in liver,kidney,stomach and small intestine were relatively higher.Furthermore,the excretions of scopoletin in bile,urine and feces were only 0.032%,3.752% and 0.784%,respectively,suggesting that scopoletin was mainly eliminated by metabolism rather than excretion as parent drug.

Study on tissue distribution of a novel organoselenium antitumor compound WBSELEN

A novel organoselenium compound,WB（1,2-[bis（1,2-benzisoselenazolone-3（2H）-ketone）]pentane） has indicated anti-tumor activity.Its pharmacokinetic data has never been determined.By using the H22 tumor bearing mouse model,the tissue distribution of WB after single and four consecutive doses（both were 120 mg/kg/d） was explored.The selenium content of the tissues was used as an indicator of WB absorption,distribution and metabolism.The selenium in the heart,liver, spleen,kidneys,lungs,stomach,pancreas,brain,colon,intestine,testes,plasma,and tumor were determined by generation atomic fluorescence spectrometry（AFS）.With single or multiple oral administration of WB,the selenium content significantly increased in the liver,stomach,colon,and intestine.The selenium content in the spleen,lungs,pancreas,testes,plasma and tumor also increased compared with the controls;but no significant changes were found in the brain and kidney.WB and its metabolites distributed predominantly in the colon,liver,stomach and intestine,which resulted in a significant increase in the selenium content in both groups.There was no observed significant accumulation of WB in the vital organs.