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PubMed1982

[Tissue distribution of fortimicin used in the field of obstetrics].

A new aminoglycoside antibiotic, fortimicin, was administered intramuscularly at a dose of 200 mg, and the tissue distribution of the drug was investigated with time-course in the uterine fundus, uterine cervix, oviduct, endometrium and ovary. Patients who required total hysterectomy or uterine appendices resection due to uterine myoma, etc. were studied. The uterus levels of fortimicin were about 2 mcg/g at 2 hours after intramuscular administration in the uterine fundus and uterine cervix and reduced to trace after 8 approximately 9 hours. The genital organs levels of fortimicin were ranged from 0.71 to 4.6 mcg/g at 1 approximately 3 hours after intramuscular administration and then reduced to the levels of 0.79 mcg/g in the oviduct, of 0.25 mcg/g in the endometrium and of 0.45 mcg/g in the ovary after 5 hours.

Aminoglycosides↗

PubMed2006

Pharmacokinetics, tissue distribution, metabolism, and excretion of depside salts from Salvia miltiorrhiza in rats.

Salviae miltiorrhiza, a traditional Chinese medical herb known as "Danshen," has been widely used in clinics to improve blood circulation, relieve blood stasis, and treat coronary heart disease. Depside salts from S. miltiorrhiza are a novel drug in which magnesium lithospermate B and its analogs are the active components. The pharmacokinetics, tissue distribution, metabolism, and excretion of three of the major components, lithospermic acid B, rosmarinic acid (RA), and lithospermic acid (LA), were studied by liquid chromatography-tandem mass spectrometry following intravenous administration in Sprague-Dawley rats. The elimination half-lives for LSB, RA, and LA were 1.04, 0.75, and 2.0 h, respectively, when 60 mg/kg S. miltiorrhiza depside salts were administrated. The areas under the curve for LSB, RA, and LA were 51.6, 6.6, and 25.2 mg . h/l, respectively, and the values decreased in the individual tissues in the following order: kidney > lung > liver > heart > spleen > brain for LSB; kidney > lung > heart > liver > spleen > brain for RA; and heart > lung > kidney > liver > spleen > brain for LA. After intravenous administration of 60 mg/kg S. miltiorrhiza depside salts, 86% of the LSB was excreted in the bile within 6 h. The main metabolites M1 and M2 were found in the serum. Overall, the results show that depside salts from S. miltiorrhiza are rapidly and widely distributed to tissues after intravenous administration in rats but that they are also rapidly cleared and excreted.

Animals↗

PubMed1983

Tissue distribution of coumarin, 7-hydroxycoumarin and their 7-hydroxy metabolites following parenteral administration of 14C-labeled compound in the DBA/lac mouse.

The time related tissue distributions of coumarin (C), 7-hydroxycoumarin (7HC) and their metabolites were studied in DBA/lac mice following retro-orbital injection of 14C-labeled compound. The activity was determined as dpm/ml or g wet weight over a period of 120 min. C was found in blood, kidney, liver, muscle, brain, heart, lung and fat but not in the testes. Upon C dosing, 7HC was found in kidney, liver and lung; 7-hydroxycoumarin glucuronide (7HCG) was found in blood, kidney and liver; 7-hydroxycoumarin sulfate (7HCS) was found in the blood, kidney and lung. Unidentified glucuronide and sulfate metabolites were detected in blood, kidney, liver and lung. Two unidentified unconjugated metabolites were detected in the kidney and liver. Unidentified water soluble metabolites were detected in kidney, liver, muscle, heart and testes. Upon 7HC dosing only 7HC, 7HCG and 7HCS were detected in any organ. 7HC and 7HCG were found in blood, kidney, liver, muscle and lung. 7HCS was detected in blood, kidney, liver and lung. Upon both C and 7HC dosing the kidney and liver contained the highest levels of radioactivity.

Animals↗

PubMed1999

Tissue distribution and turnover of [3H]riboflavin during respiratory infection in mice.

Studies in children and mice suggest that respiratory infections cause a mobilization of riboflavin from the tissues to the blood, resulting in increased urinary loss of this vitamin. To verify this observation, the tissue distribution and turnover of [3H]riboflavin were investigated in control and low-riboflavin-fed mice infected with Klebsiella pneumoniae. Infection significantly reduced [3H]riboflavin levels in the liver and kidney of low-riboflavin-fed mice and in the liver of control mice. Such changes were not observed in tissues such as muscle, small intestine, and brain. Urinary excretion of [3H]riboflavin increased significantly during the acute phase of infection and the biological half-life of [3H]riboflavin was shorter in the low-riboflavin-fed group. The results confirm that the mobilization of riboflavin from tissues to blood during infection results in a deterioration of riboflavin status. Thus, the study supports the hypothesis that respiratory infection is a nondietary factor contributing to the high prevalence of subclinical riboflavin deficiency in children of developing countries like India.

Administration, Oral↗

PubMed2005

Influence of the route of administration on efficacy and tissue distribution of ivermectin in goat.

The tissue concentration and efficacy of ivermectin after per os and subcutaneous administration were compared in goats experimentally infected with Trichostrongylus colubriformis (ivermectin-susceptible strain, INRA). Infected goats (n = 24) were treated per os (n = 9) or subcutaneously (n = 9) with ivermectin, 0.2 mg/kg, or kept as not treated controls. The faecal egg counts and small intestine worm counts were determined. Ivermectin concentration was measured in the plasma, gastrointestinal tract, lung, skin or hair, liver and adipose tissues at 0, 2, 7 and 17 days post-treatment. The efficacy of ivermectin against T. colubriformis infection in goat was 98.7 and 99.9% for subcutaneous and oral administration, respectively. Ivermectin concentration declined with time and only residual concentration was measured at 17 days post-treatment in plasma and gastrointestinal tract. Ivermectin concentration was higher after subcutaneous compared to per os injection in most of the tissue examined. In skin, hair and subcutaneous adipose tissue ivermectin persisted at significant concentrations 17 days post-treatment for both routes of administration. In our experimental conditions, ivermectin provides similar efficacy against T. colubriformis after subcutaneous or per os administration in goat. However, the lower ivermectin levels in tissues after per os administration suggest that the lasting of efficacy may be shortened after per os compared to subcutaneous administration especially in animals with poor body condition in pasture where re-infection occurs quickly after anthelmintic treatment.

Administration, Oral↗

PubMed1999

Comparison of 225actinium chelates: tissue distribution and radiotoxicity.

The biodistribution and tissue toxicity of intravenously administered 225-actinium (225Ac) complexed with acetate, ethylene diamine tetraacetic acid (EDTA), 1, 4, 7, 10, 13-pentaazacyclopentadecane-N, N', N", N"', N""-pentaacetic acid (PEPA), or the "a" isomer of cyclohexyl diethylenetriamine pentaacetic acid (CHX-DTPA), were examined. The percent of injected dose per organ and per gram of tissue for each chelate complex was determined. 225Ac-CHX-DTPA was evaluated further for radiotoxic effects. Mice receiving > or =185 kBq 225Ac-CHX-DTPA suffered 100% morbidity by 5 days and 100% mortality by 8 days postinjection, and all animals evaluated had significant organ damage. The in vivo instability of the 225Ac-CHX-DTPA complex likely allowed accumulation of free 225Ac in organs, which resulted in tissue pathology.

Actinium↗

PubMed1993

Effects of metastatic and non-metastatic mammary adenocarcinoma on tissue distribution of gallium-67 in the rat.

The purpose of this work was to study the effect of metastatic and non-metastatic mammary adenocarcinoma on tissue distribution of gallium-67 (67 Ga) citrate in Fischer-344 female rats by the use of gamma counting techniques. The homogenate (0.1 mm) of a sample of metastatic and non-metastatic tumor was implanted by subcutaneous injection in the right footpad of each animal's hind extremity. The animals bearing metastatic tumor were studied 2-24 days and the non-metastatic group 2-30 days after the implantation of tumor homogenate. The control group consisted of four animals and tumor-bearing groups of seven to eight animals at each time point. All animals were injected with 1.11 MBq of 67Ga citrate by intravenous administration and sacrificed in halothane anesthesia 48 h later. The relative tissue uptake data are presented as arithmetical mean value with a standard error and graphically demonstrated as normalized data with respect to control. The results demonstrate that 67Ga citrate uptake was largely unaffected in most organs by the presence of either metastatic or non-metastatic tumor. Gallium-67 uptake, however, was significantly and consistently increased in the popliteal lymph nodes of the ipsilateral extremity of tumor implant in the metastatic group. No difference was observed in the non-metastatic tumor group. The findings of this experimental work indicate that the host reaction to the tumor does not modify the gallium uptake characteristics in the normal tissues of tumor-bearing animals.

Adenocarcinoma↗

PubMed1983

Adipose tissue content as a modifier of the tissue distribution, biological effects, and excretion of a hexachlorobiphenyl in C57BL/6J and DBA/JBOMf mice.

C57BL/6J (C57) and DBA/JBOMf (DBA) mice were used to study the role of adipose tissue as a modifier of tissue distribution, biological effects, and elimination of a lipophilic foreign chemical, 2,4,5,2',4',5'-hexachlorobiphenyl (HCB). As an indication of biological potency of the model compound, the activities of hepatic drug-metabolizing enzymes were determined. DBA mice contained twice as much body fat as C57 mice. Since the highly lipophilic HCB was primarily sequestered by the adipose tissue, DBA mice required greater doses of HCB than did C57 mice to reach similar tissue levels of the chemical. Accordingly, greater HCB doses were required by DBA mice for elevation of drug-metabolizing enzyme activities. Phenobarbital elevated enzyme activities in a similar way in both mouse strains. When the dietary intake of DBA mice was restricted, the body fat content decreased from 15% to 5% of body weight during 1 week. In these animals the tissue accumulation of HCB and enzyme induction resembled the situation in C57 mice fed ad libitum. Highest elevations were seen in the activities of 7-ethoxycoumarin-O-deethylase and arylhydrocarbon hydroxylase (EC 1.14.14.2). In addition, the activity of epoxide hydrolase (EC 3.3.2.3) was increased, whereas glutathione S-transferase as well as UDP-glucuronosyltransferase (EC 2.4.1.17) activities remained unchanged. The abundant adipose tissue content played no role in the nonresponsiveness of DBA mice to 3-methylcholanthrene since, in contrast to C57 mice, no changes in enzyme activities were detected in DBA mice deprived of food, even after large doses of 3-methylcholanthrene. The adipose tissue content also affected the rate of elimination of HCB. DBA mice excreted smaller quantities of HCB than did C57 mice after equal doses. When, however, fasted DBA mice received HCB, they excreted it at rates similar to those of C57 mice fed ad libitum. In C57 mice, concomitant to the elevation of monooxygenase activities, there was an increase in the rate of excretion of HCB. No such elevation could be seen after a dose that was too small to elevate enzyme activities.

Adipose Tissue↗

PubMed1977

[Tissue distribution of native and enzyme-treated human immunoglobulin (author's transl)].

The tissue distribution of intravenously injected native and enzyme-treated human gammaglobulin has been investigated in the small intestine, kidney, striated muscle and the salivary gland of the mouse. Peroxidase-as well as FITC-labeled antibodies to human gammaglobulin were used to locate the injected antibody preparation. With this assay, the enzyme-treated immunoglobulin was found intracellularly, whereas the intact molecule seemed not to penetrate the cell wall and could mostly be found intra-and perivascularly. Since highly purified tetanus toxoid was fixed by thin sections of the intestine tissue containing intracellularly located enzyme-treated gammaglobulin it is concluded that the antibodies penetrating the cell wall retain their biological activity.

Animals↗

PubMed1984

The human glutathione S-transferases: studies on the tissue distribution and genetic variation of the GST1, GST2 and GST3 isozymes.

Three sets of isozymes of glutathione-S-transferase (GST) have been identified in human tissues. They differ in their tissue distribution, incidence of genetic variation, susceptibility to inactivation by N-ethylmaleimide and in their electrophoretic mobilities. The GST1 isozymes exhibit four phenotypes, including a common 'null' phenotype attributable to different combinations of three autosomal alleles GST1 1, GST1 2 and GST1 0 of frequency 0.13, 0.23 and 0.64, respectively, in the European population. The genetic polymorphism of GST1 is easily demonstrable in adult liver, kidney, adrenal and stomach but the isozymes are only weakly expressed in skeletal and cardiac muscle and not at all in fetal liver, fibroblasts, erythrocytes, lymphocytes and platelets. The GST2 isozymes also exhibit variant patterns but these are probably due to post-synthetic modification rather than allelic variation. The GST2 isozymes are not detectable in erythrocytes, platelets, cultured fibroblasts or lymphocytoid cells but are found in many other tissues, including fetal liver. GST3 isozymes were found as relatively strong components in every tissue examined except adult liver, with slight tissue to tissue variability in electrophoretic mobility.

Adrenal Glands↗

PubMed1993

Tissue distribution of two NMDA receptor antagonists, [3H]CGS 19755 and [3H]MK-801, after intrathecal injection in mice.

The tissue distribution of [3H]cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755) and [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (NK-801) was investigated after a single IT injection into lumbar spinal cord of mice. The level of radioactivity was analyzed in the lumbar, thoracic, and cervical spinal cord, brainstem, frontal cortex, liver, lungs, kidneys, stomach, intestine, spleen, heart, and blood from 5 min up to 6 h after injection. Within the CNS, [3H]CGS 19755 redistributed slowly from the site of injection toward the brainstem and cortex, peaking in the cortex 3-4 h after IT injection. At no time, however, did the relative level per gram of tissue in the frontal cortex exceed 10% of the relative level in the lumbar region of the spinal cord. The highest peripheral level of [3H]CGS 19755 was found in the kidneys. [3H]MK-801 redistributed rapidly from the spinal cord injection site to the peripheral organs. The highest peripheral levels of [3H]MK-801 were found in the lungs and liver, where the radioactivity peaked at 10 and 30-60 min, respectively, after injection. The relative levels of [3H]CGS 19755 were consistently higher in CNS tissues (except for the first 15 min in the frontal cortex) and blood than the corresponding levels of [3H]MK-801. The opposite relationship was true in the liver, lungs, kidneys, stomach, intestine, spleen, and heart. The effect on the response latency in the hot-plate test was quantified in the same animals immediately prior to sacrifice for the distribution study.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2000

Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin: pharmacokinetics and tissue distribution after i.v. administration to rats.

Non-stealth and stealth solid lipid nanoparticles (SLN) carrying doxorubicin were prepared as drug delivery systems. The pharmacokinetics and tissue distribution of doxorubicin in these SLN were studied after i.v. administration to conscious rats and were compared to the commercial solution of doxorubicin. The same dose of each formulation (6 mg kg(-1)of body weight) of doxorubicin was injected in the rat jugular vein. Blood samples were collected after 1, 15, 30, 45, 60 min and 2, 3, 6, 12, and 24 h after the injection. Rats were sacrificed after intervals of 30 min, 4 h, and 24 h and samples of liver, spleen, heart, lung, kidney, and brain were collected. In all samples, the concentration of doxorubicin and of the metabolite, doxorubicinol, were determined. Doxorubicin and doxorubicinol were still present in the blood 24 h after injection of stealth and non-stealth SLN, while they were not detectable after the injection of the commercial solution. The results confirmed the prolonged circulation time of the SLN compared to the doxorubicin solution. In all rat tissues, except the brain, the amount of doxorubicin was always lower after the injection of the two types of SLN than after the injection of the commercial solution. In particular, SLN significantly decreased the heart concentration of doxorubicin.

Animals↗

PubMed1996

Tissue distribution and pharmacokinetics of centchroman. A new nonsteroidal postcoital contraceptive agent and its 7-desmethyl metabolite in female rats after a single oral dose.

This study reports assay methodology, tissue distribution, and the basic pharmacokinetic behavior of centchroman and its 7-desmethyl metabolite [7-desmethyl centchroman (DMC)] after a single 12.5 mg/kg po dose in young female rats. Plasma, liver, lung, spleen, uterus, and adipose tissue were collected at various time intervals up to 14 days after dose. Reversed-phase HPLC, coupled with fluorescence detector, was used for simultaneous determination of centchroman and DMC in biosamples. The drug and metabolite were quantitated up to 2 and 5 ng/ml in plasma and 10 and 20 ng/g in tissues, respectively. The assay method was validated in terms of accuracy, precision, interassay, and intraassay variability, and was found to be reliable and reproducible. Peak centchroman levels in all of the tissues were found between 8-12 hr, whereas DMC peaks appeared between 8 and 24 hr, except that in liver the first peak of 1.2 micrograms/g appeared in the 1-hr sample. Tissue-to-plasma concentration ratios of centchroman were > 200 times in the lung; > 100 times in the spleen, liver, and adipose tissue; and > 40 times in the uterus at maxima in each tissue. Similarly, tissue concentrations of DMC were > 350 times in the lung, > 100 times in the liver and spleen, and > 25 times in the uterus and adipose tissue than in the plasma. High tissue-to-plasma concentration ratios of metabolites than the parent drug are indicative of its greater affinity for tissues. Terminal half-life of the centchroman and DMC in plasma were 24.1 and 36.6 hr, respectively. The mean residence time of centchroman was highest in the liver (78.4 hr), followed by the uterus (72.7 hr), adipose tissue (47.5 hr), lung (46 hr), spleen (44.1 hr), and plasma (37.7 hr). The mean residence time of DMC was also highest in the liver (133.7 hr), followed by the uterus (122 hr), adipose tissue (85.2 hr), lung (62.6 hr), spleen (62.6 hr), and plasma (48.2 hr).

Administration, Oral↗

PubMed2001

Tissue distribution, excretion, and metabolism of 1,2,7,8-tetrachlorodibenzo-p-dioxin in the rat.

A tissue distribution, excretion, and metabolism study was conducted using a relatively non-toxic dioxin congener, i.e., 1,2,7,8-tetrachlorodibenzo-p-dioxin (1278-TCDD), to gain a better understanding of mammalian metabolism of dioxins. Conventional, bile duct cannulated, and germ free male rats were administered mg/kg quantities as a single oral dose. Elimination of 1278-TCDD was largely complete by 72 h. Distribution of [14C]1278-TCDD was low in all tissues examined. Metabolites were identified in urine, bile, and feces by negative ion FAB-MS and 1H-NMR, or GC/MS. The major fecal metabolite was a NIH-shifted hydroxylated TCDD. The bile contained a glucuronide conjugate of this hydroxy TCDD, and a diglucuronide conjugate of a dihydroxy-triCDD. The major metabolites in urine were glucuronide and sulfate conjugates of 4,5-dichlorocatechol.

Animals↗

PubMed1996

Effect of magnesium supplementation and training on magnesium tissue distribution in rats.

The aim of this work is to study the effect of training and Mg supplementation on body pools of Mg and on Mg tissue distribution. Forty male Wistar rats were divided into four groups (n = 10): control group (C); trained group (T); Mg-supplemented group (+Mg); and trained and Mg-supplemented group (+MgT). The Mg supplement (1000 ppm of Mg) was given in the drinking water for 21 d. The training consisted of swimming during 60% of maximal swimming time obtained in the first session to exhaustion, during 3 wk (5 d a week). The variables measured were: erythrocytes (RBC), hemoglobin (Hb), hematocrit (Hto), total proteins (TP), and Mg in serum, RBC, liver, muscle, bone, and kidney. There was less Mg in liver, muscle, and erythrocyte in trained animals than in control or supplemented animals (T vs C, +MgT vs C and +MgT vs +Mg) (p < 0.01). Trained animals (T and +MgT) showed higher Mg kidney rates than the untrained ones (p < 0.01). There was less bone Mg in control (C) and in supplemented and trained (+MgT) groups than in trained (T) and in supplemented (+Mg) animals (p < 0.01). Serum Mg showed a decreasing concentration profile in the following order: +Mg, +MgT, T, C (p < 0.01). We conclude that Mg supplementation improves bone and serum Mg levels, but this does not affect Mg status in soft tissues. Maintained exercise leads to a diminution of Mg in the aforementioned soft tissues that is not noticeable in serum, probably provoked by an increase of renal excretion.

Analysis of Variance↗

PubMed2003

Tissue distribution, excretion and metabolism of o-anisidine in rats.

OBJECTIVES: The principal commercial use of o-anisidine is believed to be as an intermediate in the manufacture of dyes. It has also been reported to be an intermediate in the manufacture of synthetic guaiacol and its derivatives. o-Anisidine is an urinary bladder carcinogen in mice and rats. The aim of the study was to investigate the kinetics of body distribution, excretion and biotransformation of o-anisidine in rats following a single, intraperitoneal administration. MATERIALS AND METHODS: The tissue distribution and excretion of o-anisidine following i.p. administration of a single dose of 10 mg/kg was investigated using radiotracer [3H]. Metabolism of o-anisidine was investigated in the rats following i.p. administration of a single dose of 50 mg/kg using GC/MS technique. RESULTS: After 72 h, about 72% of the given dose was excreted in urine. As indicated, urine proved to be the main route of tritium excretion. In all examined tissues, the highest concentrations of tritium were found 12 h after injection and the highest accumulation was detected in the liver, kidneys and in the muscle tissue. In urine, the following substances were identified and quantified by GC peak areas: N-acetyl-2-methoxyaniline and N-acetyl-4-hydroxy-2-methoxyaniline. CONCLUSIONS: Prolonged tritium retention observed in the majority of tissues indicated that o-anisidine, especially in the case of repeated exposure, might accumulate in the body. The metabolism encompasses amine group acetylation and ring oxidation.

Aniline Compounds↗

PubMed1996

The endothelin receptor is a major determinant for the nonlinear tissue distribution of the endothelin antagonist BQ-123.

The nonlinearity in the pharmacokinetics of the cyclopentapeptide endothelin antagonist BQ-123 was studied. Both the total body clearance and tissue-to-plasma concentration ratio (Kp) were investigated in rats under a wide range of steady-state plasma concentrations (Cpss) obtained by changing the intravenous infusion rate of BQ-123. The total body clearance was constant up to a Cpss level of 50 microM, although it was markedly decreased at higher Cpss values, which suggests the existence of a saturable elimination mechanism. A Cpss-dependent nonlinearity in the apparent Kp values (Kp,app) was clearly observed in many organs including lung, heart, spleen, pancreas, adrenal, stomach, intestine, colon, aorta, testis and muscle, where the endothelin ET(A) receptor is known to be localized. By fitting the saturation curves of the Kp,app values, a similar dissociation constant (Kd) was obtained for most organs at 5 to 10 nM, which is close to the reported Kd values of BQ-123 for the endothelin ET(A) receptor. The saturable portion of the Kp,app values observed in vivo showed a good correlation with reported values of the endothelin ET(A) receptor density. Binding of BQ-123 to isolated membrane fractions from several organs demonstrated clear saturability for the lung, heart, spleen and liver with Kd values of 1 to 3 nM. Such specific binding also showed a good correlation with the saturable portion of the Kp,app values. From these results, we concluded that the endothelin receptor(s) is responsible for the nonlinear tissue distribution of BQ-123 in rats.

Animals↗

PubMed2005

Tissue distribution, synthesis stage, and ethylene induction of pineapple (Ananas comosus) chitinases.

We examined the tissue distribution, synthesis stage, and ethylene induction of three types of pineapple chitinase using chitinase activity gel and immunoblot analysis. Type A (acidic class III) exists in all tissues, while type B (weakly basic class I, which has strong antifungal activity) and type C (acidic class I) are localized mainly in the leaf and stem. In a pericarp, type A exists at all stages during fruit development, while type B and type C exist only at the early stage. Synthesis of type A is induced by ethylene, while that of types B and C is not affected by it. These results suggest that the physiological roles of these three types of chitinase in pineapple are different.

Ananas↗