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PubMed1995

Pharmacokinetics of human activated protein C. 2nd communication: tissue distribution study of a lyophilized purified human activated protein C after single or repeated intravenous administration in male mice and placental transfer and milk passage study after intravenous administration in pregnant and lactating mice.

Tissue distribution studies of human activated protein C (CAS 42617-41-4, APC) were performed in mice after single or repeated administration, and placental transfer and milk passage study were investigated. At 15 min after a single intravenous administration of 125I-APC, radioactivity was mainly distributed to the blood and blood rich organ, such as liver, and then rapidly eliminated. The radioactivity distributed to tissues was almost negligible at 24 h after administration except for the thyroid. The qualitative study of the distribution of radioactivity to tissues by whole body autoradiography demonstrated the correspondence to the result of the quantitative assay of distribution of radioactivity after single administration of 125I-APC. The influence of repeated administration of APC on its pharmacokinetic disposition was studied by administering 125I-APC once a day to mice for 14 days. Though plasma radioactivity at 15 min in mice during repeated administration of 125I-APC was almost similar to that at 15 min after a single administration, the radioactivity at 24 h after administration was 2 times higher than that after a single administration. The profile of plasma radioactivity during and after repeated administration corresponded to the simulation curve which was described with the pharmacokinetic parameters obtained previously after the single administration. Distribution profile after repeated administration at 15 min after the 4th, 7th, 10th and 14th administration was almost similar to that at 15 min after a single administration except for the thyroid and spleen. In the thyroid, the radioactivity was 500 times higher than that after a single administration, and HPLC analysis demonstrated that the radioactivity was attributed to thyroglobulin. As to the spleen, the radioactivity was about 52% of that after a single administration. During the repeated administration, the spleen became larger than that after a single administration and the final weight was 2 times heavier than that of the non-treated animal. The decrease in radioactivity of the spleen during repeated administration was attributed to the hypertrophy of the organ. Placental transfer of 125I-APC was studied with pregnant mice quantitatively and qualitatively. Radioactivity distributed in fetuses was low at every point examined, and the result corresponded to the autoradiography. During lactation, radioactivity transferred to milk and milk to plasma ratio reached 5.7 after intravenous administration of 125I-APC. HPLC analysis of the milk radioactivity demonstrated that most of the radioactivity was present in the macromolecules produced by the lactating mother.

Animals↗

PubMed1997

Tissue distribution of human gp330/megalin, a putative Ca(2+)-sensing protein.

We used riboprobes and monoclonal antibodies to characterize tissue distribution of the human 550-kD homologue to gp330/megalin, primarily identified in the rat kidney. Human gp330/megalin mRNA and protein are readily identified in human parathyroid cells, placental cytotrophoblasts, kidney proximal tubule cells, and epididymal epithelial cells. The immunoreactivity is found on the surface of the cells and is heterogeneously downregulated in parathyroid hyperplasia and adenomas. Cells of the proximal kidney tubule and epididymis express the protein on their luminal aspect. Moreover, the protein is expressed in Type II pneumocytes, mammary epithelial and thyroid follicular cells, and the ciliary body of the eye. Sequence analysis of cDNA fragments, obtained by RT-PCR, revealed identical nucleotide sequences in parathyroid, kidney, placenta, epididymis, and lung. Immunohistochemistry for parathyroid hormone-related protein (PTHrP) revealed partial co-expression with human gp330/megalin in parathyroid, placenta, and mammary gland. The findings substantiate human gp330/megalin expression in a variety of human tissues expected to possess calcium-sensing functions. It may constitute a protein of utmost importance to adult and fetal calcium homeostasis, although other important functions may also be coupled to this exceptionally large protein with highly restricted tissue distribution.

Amino Acid Sequence↗

PubMedDate not supplied

Absorption, tissue distribution and elimination of 4-[(3)h]-epigallocatechin gallate in beagle dogs.

Polyphenols found in tea are potent antioxidants and have inhibitory activity against tumorigenicity. The purpose of the described study was to assess the absorption, tissue distribution, and elimination of epigallocatechin gallate (EGCG), the principal catechin found in green tea, in a nonrodent species. 4-[(3)H]-EGCG was administered to beagle dogs by intravenous (IV) and oral routes. Following IV administration of 25 mg/kg, radioactivity in the bloodstream resided predominantly in the plasma. Distribution occurred during the first hour, and the plasma levels of total radioactivity declined with a mean half-life of approximately 7 hours. The apparent volume of distribution (0.65 l/kg) indicated wide distribution, and the total body clearance (1.01 ml/min-kg) was low. A subsequent single oral dose (250 mg/kg) was rapidly absorbed, with peak plasma levels at about 1 hour after administration, followed by elimination with a mean half-life of 8.61 hours. The mean area under the curve (AUC) for total radioactivity was approximately 20% of the value following IV administration (corrected for dose administered). Excretion of radioactivity in the feces predominated over urinary excretion following both IV and oral administration of [(3)H]-EGCG. Tissue distribution was determined 1 hour after an IV dose (25 mg/kg) administered after 27 days of oral treatment with EGCG (250 mg/kg/day) to mimic chronic consumption of tea. Radioactivity was distributed to a variety of epithelial tissues; the highest concentrations were observed in the liver and gastrointestinal tract tissues. Repeat dose oral administration of EGCG resulted in significantly lower blood radioactivity compared to the concentration following a single dose. These results are generally in accord with previous studies in rodents and indicate that, after oral administration, EGCG (as parent compound and metabolites) is widely distributed to tissues where it can exert a chemopreventive effect.

Administration, Oral↗

PubMed1991

Purification, some properties, and tissue distribution of a major lysosome-associated membrane glycoprotein (r-lamp-2) of rat liver.

We previously purified and characterized a major lysosomal membrane glycoprotein (r-lamp-1) from rat liver [Akasaki et al. (1990) Chem. Pharm. Bull. 38, 2766-2770]. The present study describes the purification of another major lysosomal membrane glycoprotein (r-lamp-2) from rat liver and compares the tissue distribution of r-lamp-1 and r-lamp-2 in rats. R-lamp-2 was purified to apparent electrophoretic homogeneity from rat liver by a simple method with a protein yield of approximately 4.0 micrograms/g wet weight of liver. The purification procedure includes: preparation of tritosomal membranes, extraction of tritosomal membranes with Lubrol PX, wheat germ agglutinin (WGA)-Sepharose affinity chromatography, and monoclonal antibody-Sepharose affinity chromatography. R-lamp-2 exhibited an Mr of 96,000 on SDS-PAGE and had an acidic pI of less than 3.5. R-lamp-2 contained 52.3% carbohydrates. Its carbohydrate moieties were composed of numerous sialyl complex type N-linked oligosaccharides and small amounts of O-linked oligosaccharides. Both r-lamp-1 and r-lamp-2 were detected in all rat tissues examined by immunoblot analyses, while their apparent molecular weights differed among the tissues. Immunological quantitative analysis showed that the protein concentrations of r-lamp-2 were consistently lower than those of r-lamp-1 in all the tissues tested. There was a significant correlation with a regression coefficient of 0.86 in the tissue distribution between r-lamp-1 and r-lamp-2. A good correlation was also observed in the tissue distribution between acid phosphatase and r-lamp-2.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed2005

Circadian variations in the pharmacokinetics, tissue distribution and urinary excretion of nifedipine after a single oral administration to rats.

Circadian variations in the pharmacokinetics, tissue distribution and urinary excretion of nifedipine were examined in fasted rats after administering a single oral dose at three different dosing times (08:00 am, 16:00 pm, 00:00 am). The plasma concentrations, the areas under the plasma concentration-time curve from zero to 6 h (AUC(0-6 h)) and the peak plasma concentration (C(max)) were significantly higher in the rats dosed at 08:00 am (immediately inactive), and was lower at 16:00 pm (most inactive) and 00:00 am (most active). The time to reach the C(max) (T(max)) was the shortest in the rats dosed at 08:00 am. It was very interesting to observe the double peak phenomena in the plasma concentration profiles, showing a larger peak followed by a smaller peak. There was a dosing time dependency on the tissue distribution 30 min after administration, showing a similar tendency to the pharmacokinetic behavior. However, there was no distinct dosing time dependency observed at 2 h after administration due to the extensive disposition. The cumulative urine excretion of nifedipine in the rats dosed at 08:00 am was significantly higher (about two-fold) than in those dosed at 16:00 pm and 00:00 am. The pharmacokinetics of nifedipine in the rats was consistent with that observed in human subjects in terms of the day-night clock time but the biological time was the opposite, as marked by the rest-activity cycles. These results may help to explain the circadian time-dependency of nifedipine pharmacokinetics.

Administration, Oral↗

PubMed2006

Uptake, tissue distribution, and excretion of brevetoxin-3 administered to mice by intratracheal instillation.

Brevetoxins are a family of potent lipid-soluble neurotoxins produced by the dinoflagellate Karenia brevis, the organism responsible for Florida red tide. Brevetoxins aerosolized by surf and wind produce irritation of the eyes, nose, and throat in people on or near red tide-affected beaches. The effects of chronic exposures to brevetoxins on healthy and health-compromised individuals are not known. The purpose of this study was to investigate the pulmonary uptake, tissue distribution, and excretion of polyether brevetoxin-3 in mice, a rodent model for investigating the potential systemic adverse health effects associated with repeated brevetoxin inhalation. Male CBA/CaJ mice were administered [3H]brevetoxin-3 by intratracheal instillation. Groups of 3 mice were sacrificed immediately after instillation and at 0.5, 3, 6, 12, 24, 48, and 96 h postinstillation. Four additional mice were placed into metabolism cages for excreta collection up to 168 h postinstillation. Brevetoxin-3 distributed rapidly to all tissues, with the highest initial doses in the liver and gastrointestinal tract. Elimination half-times ranged from approximately 28 h for fat, heart, intestines, kidneys, liver, and muscle to approximately 90 h for brain and testes. The total dose to tissue ranged from 39 ng brevetoxin equivalents-h/g for testes to 406 ng brevetoxin equivalents-h/g for liver. Approximately 90% of excretion had occurred within 96 h, with 11 and 64% of the initial brevetoxin dose excreted in urine and feces, respectively. These results are consistent with earlier reports of rapid absorption and widespread tissue distribution of brevetoxins in rats.

Administration, Inhalation↗

PubMed1990

Pharmacokinetics, tissue distribution, and cell localization of [35S]methionine-labeled recombinant human and murine alpha interferons in mice.

The pharmacokinetics, tissue distribution, cell localization, and penetration into tumor xenografts of recombinant [35S]methionine-labeled human alpha interferon (HuIFN-alpha) and murine alpha interferon (MuIFN-alpha) were examined in mice. Both interferons (IFNs) were removed from the blood in a rapid biphasic manner; HuIFN-alpha was cleared faster than MuIFN-alpha. Tissues were analyzed for radioactivity and over 90% of the IFNs was accounted for. The IFNs were detected predominantly in liver, kidney, gastrointestinal tract, pancreas, spleen, and lung. The levels of MuIFN-alpha compared with HuIFN-alpha were greater in the liver, spleen, and lung and less in the kidney, pancreas, and gastrointestinal tract. Heart, brain, testes, thymus, lymph nodes, fat, skin, and skeletal muscle contained much lower but measurable levels of both IFNs. There was penetration of HuIFN-alpha into tumor xenografts. The pharmacokinetics of IFN-alpha were independent of the strain of mouse, BALB/c or CBA, immune deprivation, or the presence of a tumor xenograft. Autoradiography of tissue sections from mice given injections of HuIFN-alpha or MuIFN-alpha indicated focal radioactivity in proximal convoluted tubules in the kidney and diffuse radioactivity in the liver, gastrointestinal tract, and pancrease. MuIFN-alpha, but not HuIFN-alpha, showed intense localization in cells in hepatic sinusoids, marginal zones in the spleen, and pulmonary alveolar walls, suggesting uptake by cells of the monocyte/macrophage lineage in these sites. The study shows the utility of biosynthetic labeling for pharmacokinetic studies of cytokines, clear differences in tissue distribution of IFN-alpha according to its species of origin, and targeting of homologous IFN-alpha to cells of the monocytic lineage.

Animals↗

PubMedDate not supplied

Tissue distribution and plasma pharmacokinetics of UCN-01 at steady-state and following bolus administration in rats: influence of human alpha1-acid glycoprotein binding.

The primary focus of this study was to investigate the role of human alpha1-acid glycoprotein (hAGP) on the pharmacokinetics and tissue distribution of the antitumor drug UCN-01 (7-hydroxystaurosporine) in rats, following bolus administration and at steady-state blood concentration. To evaluate plasma pharmacokinetics, the rats received UCN-01 alone, UCN-01 + hAGP (87:1 ratio), or UCN-01 + hAGP (26:1 ratio) i.v. Additional rats were studied after i.m. administration of UCN-01 and i.v. administration of human AGP (87:1 ratio). For tissue distribution, rats received UCN-01 alone, UCN-01 + hAGP (87:1 ratio). One hour after drug administration, blood samples as well as various tissues and organs were collected. Plasma concentrations of UCN-01 as well as tissue accumulation were measured by HPLC using a fluorescence detector. Following i.v. bolus administration, the UCN-01 concentration-time profile declined bi-exponentially. The distribution half-life was 0.2 hours, while the elimination half-life was 6.65 hours. The volume of distribution of the central compartment (Vc) was 1000 ml/kg and the volume of distribution during the elimination phase (Vdb) was 2551 ml/kg. The total body clearance (TBC) was 4.4 ml/min/kg. Co-administration of hAGP with UCN-01 at 1:87 ratio did not affect the elimination half-life of UCN-01 during our sampling period, however the distribution half-life was delayed by approximately 2.7-fold. Furthermore, the Vc, Vd(beta) and TBC were significantly reduced to 395 ml/kg, 735 ml/kg and 1.34 ml/min/kg, respectively. UCN-01 Vd's and TBC were reduced further by increasing human hAGP:UCN-01 ratio to 26:1. Also, hAGP administration did not significantly affect the pharmacokinetic profile of UCN-01 after i.m. administration, which was similar to that measured after i.v. administration. One hour after i.v. bolus administration, UCN-01 was distributed extensively to all tissues with a tissue/plasma ratio ranging from 10-times in the brain to more than 1000-times in the lungs. The presence of hAGP drastically reduced tissue accumulation of UCN-01, although the tissue to plasma ratio remained > 1.0 except for the brain. At steady-state blood concentration following the infusion of UCN-01 over 180 minutes, the ratio of the drug concentration to the concomitant plasma concentration remained > 1.0, even in the presence of hAGP. The data showed that the binding of UCN-01 to hAGP drastically altered its pharmacokinetics and tissue distribution, even at the plasma steady-state concentration.

Alkaloids↗

PubMedDate not supplied

Comparisons of the intraocular tissue distribution, pharmacokinetics, and safety of 125I-labeled full-length and Fab antibodies in rhesus monkeys following intravitreal administration.

Access of recombinant proteins to the retina following intravitreal administration is poorly understood. A study was conducted in male Rhesus monkeys (15 to 28 mo of age; 2.8-3.3 kg) in order to compare the intraocular tissue distribution, pharmacokinetics, and safety of 125Iodine (I)-labeled full-length humanized rhuMAb HER2 antibody (148 kD) and of 125I-labeled humanized rhuMAb vascular endothelial growth factor Fab antibody (48.3 kD) following bilateral bolus intravitreal injection on day 0 (5 animals/group). The dose administered to each eye was 25 microg (9-10 microCi) in 50 microl. Animals were euthanatized on day 0 (1 hr postdose) and on days 1, 4, 7, and 14. Safety assessment included direct ophthalmoscopy, intraocular pressure measurements, clinical observations, body weight, and hematology and clinical chemistry panels. Blood and vitreous samples were collected daily (blood only) and at necropsy for pharmacokinetics and analysis for antibodies to the test materials; the ocular tissue distribution of the test material was evaluated by microautoradiography. All animals completed the study. Microautoradiography demonstrated that the full-length antibody did not penetrate the inner limiting membrane of the retina at any of the time points examined. In contrast, the Fab antibody fragment diffused through the neural retina to the retinal pigment epithelial layer at the 1-hr time point and persisted in this location for up to 7 days. Systemic exposure to test material was low but variable: the highest plasma concentration of the full-length antibody was 20.3 ng/ml, whereas plasma concentrations for the Fab antibody remained below the limit of quantitation (i.e., <7.8 ng/ml). An immune response to the test material was not evident in either treatment group. The half-life in vitreous was 5.6 days for the full-length antibody and 3.2 days for the Fab antibody. The shorter intravitreal half-life of the Fab antibody is related to its smaller size and its significant diffusion through the retinal layers. The differences in pharmacokinetics and tissue distribution that are noted between the full-length and Fab antibodies in this study identify potential therapeutic approaches that may be exploited in specific disease conditions.

Animals↗

PubMed1991

Tissue distribution of two major components of synaptonemal complexes of the rat.

In this paper we describe an analysis of the tissue distribution of two recently identified components of synaptonemal complexes (SCs), an Mr 125,000 and an Mr 190,000 protein, in the male rat by immunoblot analysis and immunocytochemical techniques. We compared the tissue distribution of these antigens with that of two earlier identified SC components, an Mr 30,000 and an Mr 33,000 polypeptide. For this purpose we used monoclonal antibodies (Mabs) that react exclusively with SCs in lysed spermatocytes, and that recognize the above mentioned antigens specifically in immunoblots of SC proteins or of nuclear proteins from spermatocytes; these were Mab IX9D5 (anti-190,000), Mab IX5B2 (anti-125,000), Mab II52F10 (anti-30,000 + 33,000), and Mab IX8G9 (anti-30,000 + 33,000). In the immunoblot experiments, we could detect the Mr 190,000 and 125,000 antigens exclusively in blots of SC proteins or nuclear proteins from spermatocytes; these antigens were not detectable in blots of nuclear proteins from liver, brain, spermatogonia or spermatids or in blots of proteins from mitotic chromosomes or nuclear laminae. With the anti- 30,000 + 33,000 Mabs we obtained essentially the same result, except that Mab IX8G9, but not II52F10, recognizes a small amount of Mr 30,000 antigen in blots of nuclear proteins from spermatids and spermatogonia. Although this might be ascribed to contamination of the isolated spermatids and spermatogonia, we cannot exclude that a small amount of Mr 30,000 antigen is present in these cells. In the immunofluorescence analysis, the testis was the only tissue that reacted detectably with the above antibodies. Within the testis, spermatocytes and some early spermatids were the only cell types that contained detectable amounts of antigen.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Identification of mK1, a true tissue (glandular) kallikrein of mouse submandibular gland: tissue distribution and a comparison of kinin-releasing activity with other submandibular kallikreins.

The protein structure, kinin-releasing activity, and tissue distribution of four major proteinases of mouse submandibular gland (mK22, mK9, proteinase F, proteinase P) were studied. When compared with the deduced amino acid sequence of each member of the tissue (glandular) kallikrein gene family, the amino acid sequence of proteinase F determined (approximately 40% of the total) was found to agree completely with the deduced amino acid sequence of mKlk-1. The proteinase P sequence, on the other hand, agreed with that of the product of mKlk-13, mK13 (prorenin-converting enzyme). Proteinase F had the strongest kininogenase activity for both low-molecular-weight and high-molecular-weight kininogen, while mK22 had 1/6 and 1/50 the activity of proteinase F for the respective kininogen substrate. Kininogenase activities of mK9 and proteinase P were less than 1/100 of the activity of proteinase F for both substrates. Acting on the two kininogen substrates, kallikreins mK22, mK9, and proteinase F, but not proteinase P, specifically released bradykinin, suggesting that the former three kallikreins strictly recognized peptide sequences around bradykinin in these substrate molecules but proteinase P recognized several sites in these molecules. Significant amounts of proteinase F, but not mK22 and others, were present in the urine, pancreas and digestive organs, as well as in the salivary glands. The present results revealed that the former proteinase F is identical to mK1, tissue/renal kallikrein, and confirmed its characteristics as a true kallikrein on the basis of its kinin-releasing activity and tissue distribution.

Amino Acid Sequence↗

PubMed1987

Tissue distribution and elimination of trichlorobenzenes in the rat.

The tissue distribution and excretion of three trichlorobenzene isomers (TCB) were investigated in the rat. Single doses of TCBs were administered orally to groups of 5 fasted rats at 10 mg/kg body weight. Serial sacrifices were carried out and the radioactivity contents were determined in tissues and blood. For all three TCB isomers, radioactivity appeared in the blood and tissues at 0.5 h, and peaked around 2-4 h after dosing. Fat, skin, and liver had high concentrations of the parent compound while kidney and muscle had high levels of metabolites. Elimination of TCB from tissues and blood can best be described by a two-compartmental open pharmacokinetic model. The terminal half-lives were 145, 93 and 68 h for 1,2,3-, 1,2,4 and 1,3,5-TCB isomer respectively. Ninety-five percent of the administered 1,2,3- and 89% of the 1,3,5-isomers were eliminated within 48 h in the urine and feces with the former being the major route.

Animals↗

PubMed1988

Tissue distribution and developmental expression of protein kinase C isozymes.

Protein kinase C is a ubiquitous enzyme found in a variety of mammalian tissues and is especially highly enriched in brain and lymphoid organs. Based on biochemical and immunological analyses, we have identified three types of protein kinase C isozyme (designated types I-III) from rat brain. Monospecific antibodies against each of the protein kinase C isozymes were prepared for the determination of tissue distribution, subcellular localization, and developmental changes of these enzymes. The various protein kinase C isozymes were found to be distinctively distributed in different tissues: the type I enzyme in brain; the type II enzyme in brain, pituitary and pineal glands, spleen, thymus, retina, lung, and intestine; and the type III enzyme in brain, pineal gland, retina, and spleen. The rat brain enzymes were differentially distributed in different subcellular fractions. The type I enzyme appeared to be most lipophilic and was recovered mostly in the particulate fractions (80-90%) regardless of the EGTA- or Ca2+-containing buffer used in the homogenization. Significant amounts (30-40%) of the type II and III enzymes were recovered in the cytosolic fraction with EGTA-containing buffer. The expressions of different protein kinase C isozymes appear to be differently controlled during development. In rat brain, both type II and III enzymes were found to increase progressively from 3 days before birth up to 2-3 weeks of age and remained constant thereafter. However, the expression of the type I enzyme displayed a different developmental pattern; it was very low within 1 week, and an abrupt increase was observed between 2 and 3 weeks of age. In thymus, the type II enzyme was found to be maximal shortly after birth; whereas the same kinase in spleen was very low within 2 weeks of age, and a significant increase was observed between 2 and 3 weeks. These results demonstrate that protein kinase C isozymes are distinctively distributed in different tissues and subcellular locales and that their expressions are controlled differently during development.

Animals↗

PubMed1998

Tissue distribution of sex steroids: concentration of 17beta-oestradiol and cyproterone acetate in selected organs of female Wistar rats.

The tissue distribution of 17beta-oestradiol and cyproterone acetate was investigated after intravenous and intragastric administration to female Wistar rats by measuring the time course of the concentration of the sex steroids in plasma, liver, kidney, brain, and heart by radioimmunoassay. Test substances were administered intravenously in doses of 0.1 mg/kg each and intragastrically in doses of 10 mg/kg (17beta-oestradiol) and 0.1 mg/kg (cyproterone acetate) corresponding to the expected oral bioavailability. Tissue distribution was assessed within each mode of administration by AUCorgan/AUCplasma-quotients (Q-values), and between both routes of administration by F-values representing (bio- and organ availability) and R-values, which express the organ load after intragastric compared to intravenous administration if the same amount of drug has been made bioavailable in the plasma after both routes (for explanation see next page). The absolute bioavailability of 17beta-oestradiol after intragastric administration of 10 mg/kg was ca. 8%. The oestradiol liver load after intragastric administration was about 20 times higher than after intravenous administration, whereas the drug load of other organs was independent of the administration route. Cyproterone acetate was completely bioavailable after intragastric administration in a dose of 0.1 mg/kg. Cyproterone acetate levels and AUC-values in all organs investigated were higher when compared to the plasma with highest levels in the liver. The organ distribution of cyproterone acetate including the drug liver load was independent of the route of administration.

Androgen Antagonists↗

PubMed1998

Quantitative comparison of autoradioluminographic and radiometric tissue distribution studies using carbon-14 labeled xenobiotics.

The tissue distribution of two 14C drugs were quantitatively compared using the techniques of whole body autoradioluminography (WBAL) and radiometry. Quantitative analysis of tissue radioactivity in whole body cryosections was accomplished from storage phosphor images using the MicroComputer Imaging Device. After obtaining whole body sections from four frozen rats and three frozen ferrets, each WBAL-sectioned specimen was partially thawed before obtaining tissue samples for radiometric analysis. For all tissues examined, concentrations of radioactivity determined by WBAL were comparable with those determined by dissection and liquid scintillation analysis (DLSA), except for renal tissue obtained from different kidneys of the same ferret and for rat ocular tissues. A 2-fold difference was observed between WBAL and DLSA evaluations of radioactivity in the contralateral kidneys of one ferret. DLSA evaluation only provided an assessment of total radioactivity in the eye, whereas WBAL evaluation determined the selective distribution of radioactivity to ocular tissues. Resolution in DLSA evaluation of ocular tissues was restricted by limitations of the dissection procedure. These results indicated that the quantitation of tissue radioactivity by WBAL was as precise as DLSA evaluation, and WBAL also provided results to the quantitative distribution of radioactivity to localized sites in organs not feasible by DLSA.

Administration, Oral↗

PubMed1984

Tissue distribution of hydrazine and its metabolites in rats.

The tissue distribution and the urinary excretion of hydrazines, hydrazine, acetylhydrazine and 1,2-diacetylhydrazine, were determined by mass fragmentography using a gas chromatography-mass spectrometer equipped with a multiple ion detector-peak matcher. Using the compounds labeled with a stable isotope as an internal standard, namely the isotope dilution method, made it possible to estimate trace amounts of hydrazine and its metabolites in the tissues. Significantly high levels of all hydrazines were detected in the kidney. Especially, acetylhydrazine, a metabolite of hydrazine, accumulated to a great extent in the kidney. Free hydrazine which was liberated from acetylhydrazine was detected both in the tissues and in the urine after the administration of acetylhydrazine. This demonstrates clearly that the metabolic pathway between hydrazine and acetylhydrazine is reversible.

Acetylation↗

PubMed1975

Tissue distribution of EDTA encapsulated within liposomes of varying surface properties.

Liposomes containing ethylenediaminetetraacetic acid (EDTA) were prepared with different surface properties by varying the liposomal lipid constituents. Positively charged liposomes were prepared with a mixture of phosphatidylcholine, cholesterol, and stearylamine. Negatively charged liposomes were prepared with a mixture of phosphatidylcholine, cholesterol, and phosphatidylserine. Neutral liposomes were prepared with phosphatidylcholine alone, dipalmitoyl phosphatidylcholine alone, or with a mixture of phosphatidylcholine and cholesterol. Distribution of 14C-labeled EDTA were determined in mouse tissues from 5 min to 24 h after a single intravenous injection of liposome preparation. Differences in tissue distribution were produced by the different liposomal lipid compositions. Uptake of EDTA by spleen and marrow was highest from negatively charged liposomes. Uptake of EDTA by lungs was highest from positively charged liposomes; lungs and brain retained relatively high levels of EDTA from these liposomes between 1 and 6 h after injection. Liver uptake of EDTA from positively or negatively charged liposomes was similar; the highest EDTA uptake by liver was from the neutral liposomes composed of a mixture of phosphatidylcholine and cholesterol. Liposomes composed of dipalmitoyl phosphatidylcholine produced the lowest liposomal EDTA uptake observed in liver and marrow but modrate uptake by lungs. Tissue uptake and retention of EDTA from all of the liposome preparations were greater than those of non-encapsulated EDTA. The results presented demonstrate that the tissue distribution of a molecule can be modified by encapsulation of that substance into liposomes of different surface properties. Selective delivery of liposome-encapsulated drugs to specific tissues could be effectively used in chemotherapy and membrane biochemistry.

Animals↗

PubMed1985

[Evaluation of the clinical effect and tissue distribution of cefpimizole in the field of gynecology].

Cefpimizole (AC-1370) was administered to 5 cases with uterine myoma before hysterectomy, and tissue distribution was determined. AC-1370 was also administered to 5 cases with gynecological infections. The following results were obtained. One gram of AC-1370 was administered from 43 to 299 minutes before hysterectomy, tissue distribution of AC-1370, such as ovary, oviduct, myometrium, cervix uteri, and portio vaginalis was showed the highest level (30.0 approximately 49.5 micrograms/g) at 43 minutes after administration, and these were 39.0 approximately 64.4% of the concentration in uterine arterial blood. Tissue concentration of AC-1370 was then gradually decreased following with the decreasing of the concentration in uterine arterial blood. AC-1370 was administered to 3 cases with pyometra, 1 case with Bartholin abscess, 1 case with adnexitis. The clinical efficacy was good in all 5 cases. Bacteriological study revealed that A. faecalis and E. coli were eradicated, but B. fragilis was persisted. No side effect was observed in all cases.

Adult↗