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At least 145 records · Page 8Linked to original sources

PubMed1977

Nocardicin A, a new monocyclic beta-lactam antibiotic VI. Absorption, excretion and tissue distribution in animals.

The absorption, excretion and tissue distribution of nocardicin A, a new monocyclic beta-lactam antibiotic, were studied in various animals. When nocardicin A was given intramuscularly in single doses of 20 mg/kg to rats, rabbits, and dogs, the peak serum levels of nocardicin A were about 1.6 similar to 2.8 times higher than those of carbenicillin in all animals though the levels varied among the species tested. The serum half-life of nocardicin A in these animals was about twice that of carbenicillin. The 24-hour urinary recovery rate of nocardicin A after intramuscular injection was 68.5 percent in rabbits and 77.0 percent in dogs, but was low in rats; i.e., 0.7 percent. When nocardicin A was given intravenously in single doses of 20 mg/kg to these animals, the peak serum levels varied widely among the test species; i.e. about 3 times higher than those of carbenicillin in rabbits and dogs, similar to those in rats. The peak serum and tissue levels of nocardicin A after intramuscular to intravenous injection were the highest in the kidneys, followed by the liver, serum, lungs, heart and spleen. The levels in the liver were prolonged. Nocardicin A, and traces of unknown substances less active than nocardicin A were observed as active substances in the urine recovered after injection of nocardicin A.

Administration, Oral↗

PubMed1990

Effect of cholesterol in various liposomal compositions on the in vivo toxicity, therapeutic efficacy, and tissue distribution of amphotericin B.

The effect of cholesterol in neutral, positively and negatively charged liposomes on the toxicity, therapeutic efficacy, and alteration in the tissue distribution pattern of amphotericin B (Amp-B) in normal and infected mice was studied. It was observed that inclusion of cholesterol (CHOL) into egg phosphatidylcholine (EPC) liposomes increased the LD50 of Amp-B from 5.3 to 8.5 mg/kg body weight. In the case of phosphatidylserine (PS) liposomes as well as stearylamine (SA) liposomes, cholesterol incorporation had no effect in altering the toxicity of the drug. The survival pattern of animals with all types of liposomal formulation of Amp-B was similar. The tissue distribution studies indicated that in the case of normal mice, cholesterol inclusion in all types of liposomes increased the organ concentration of the drug in various tissues. In infected animals, the concentration of Amp-B in all organs was increased when cholesterol was included in EPC and EPC/PS liposomes. The organ concentration of Amp-B in lung and liver after 1 h of injection was the same in the case of EPC/SA and EPC/SA/CHOL liposomes. Considering the observations on toxicity, therapeutic efficacy, and tissue distribution, it was suggested that cholesterol had a beneficial therapeutic effect on neutral EPC liposomes.

Amphotericin B↗

PubMed1990

Plasma clearance and tissue distribution of recombinant human platelet-derived growth factor (B-chain homodimer) in rats.

125I-labeled human recombinant platelet-derived growth factor (B-chain homodimer; rHuPDGF-BB) was intravenously injected into male rats, and plasma clearance and tissue distribution of total and acid-insoluble radioactivity were determined. Insoluble radioactivity was rapidly cleared from plasma in a biphasic manner with estimated distribution and elimination half-lives of 5.2 and 68 min, respectively. Less than 10% of the injected radioactivity remained in plasma at 1 hr after injection. rHuPDGF-BB was widely distributed throughout body tissues. However, acid-insoluble radioactive concentrations greater than those in plasma were only observed in liver, kidneys, and spleen. The radioactive concentration of most tissues declined rapidly between 1 and 4 hr but increased in the intestinal contents. Radioactive concentrations decreased in all tissues and intestinal contents at 8 and 24 hr. Urine samples collected at the latter interval showed that 39% of the dose was excreted by the kidneys in an acid-soluble form. These results suggest that the rapid clearance of rHuPDGF-BB from plasma is the result of widespread tissue distribution, metabolism by the liver, and excretion by the kidneys. In this respect, the pharmacokinetic behavior of rHuPDGF-BB resembles that of other lymphokines and growth factors that have recently been studied.

Animals↗

PubMed1986

Quantitative analysis of tissue distribution of Ly10-like murine alloantigen(s) with antisera and monoclonal antibodies.

Tissue distribution of non-Lyt1.1 ("Ly10-like") antigen or antigens encoded by short chromosomal segment differentiating B6-Ly-1a congenic strain from B6 strain of mice was studied by quantitative absorption of (BALB/c X B6)F1 anti B6-Ly-1a antiserum and by direct cytotoxicity of Ly-10-132-12-26 monoclonal antibody on lymphoid cell populations. Identical strain but not tissue distribution pattern does not allow to conclude whether antiserum and monoclonal antibody detect the same or closely linked antigens. Absorption experiments revealed the highest antigen content in the brain tissue, lower in testis and kidney, still lower in lymphoid organs and the lowest in liver and lung. Among lymphoid cells, bone marrow cells had highest absorbing capacity, followed by thymus, spleen and lymph nodes. Monoclonal antibody lysed almost 100% of thymocytes, 30% bone marrow cells and 10-20% of spleen and lymph node cells (both T-cell and B-cell enriched populations contained the same proportion of positive cells). Cortisone resistant thymocytes showed the same sensitivity as cortical thymocytes to Ly-10-132-12-26 antibody which is distinguishable characteristics of medullary thymocytes from peripheral T cells. Mitogen activated lymphocytes exhibited significantly higher expression of Ly10-like antigen than resting peripheral lymphocytes.

Animals↗

PubMed1986

Clearance and tissue distribution of fibronectin in septic rats: relationship to synthetic rate.

Fibronectin is a glycoprotein found in a soluble form in plasma and in an insoluble form in many tissues. We evaluated the influence of postoperative intraperitoneal sepsis on the clearance, tissue distribution, and synthesis of plasma fibronectin in rats (300-400 g). Experimental sepsis was induced by cecal ligation following laparotomy, whereas control animals underwent laparotomy (5 cm) alone. At 24 and 48 h after laparotomy, plasma fibronectin levels were normal. After laparotomy plus cecal ligation, plasma fibronectin increased by 47% at 24 h and remained elevated (52% above 0 time) at 48 h. At 24 h postsurgery the disappearance and tissue distribution of 75Se-plasma fibronectin and 75Se-plasma albumin was evaluated. Tissue distribution was quantified at 2 and 24 h after intravenous injection of both tracer proteins in separate groups. Both fibronectin and albumin demonstrated an initial distribution between vascular and extravascular sites and then a progressive decrease in plasma. In control (laparotomy) rats the half-life (t1/2) for plasma clearance of 75Se-plasma fibronectin was 25.33 +/- 2.53 h compared with 13.21 +/- 0.78 h in the septic rats. Septic rats manifested decreased sequestration of 75Se-fibronectin at the area of surgical incision (laparotomy), increased sequestration at the focus of intraperitoneal infection, and increased uptake in the nonviable portion of the cecum. The synthetic rate for plasma fibronectin in laparotomized control rats was 3.03 +/- 0.29 mg X 100 g-1 X 24 h-1, whereas after laparotomy plus cecal ligation the synthetic rate increased to 4.58 +/- 0.35 mg X 100 g-1 X 24 h-1. In contrast the synthetic rate for albumin decreased from 84.70 +/- 1.66 mg X 100 g-1 X 24 h-1 in controls to 52.38 +/- 1.77 mg X 100 g-1 X 24 h-1 in the septic animals. Thus intraperitoneal sepsis in the rat will enhance the vascular clearance, alter the distribution, and increase the synthetic rate for plasma fibronectin.

Animals↗

PubMed1994

Relation between BglII polymorphism in 3beta-hydroxysteroid dehydrogenase gene and adipose tissue distribution in humans.

The aim of this study was to investigate the association between a restriction fragment length polymorphism (RFLP) at the 3beta-hydroxysteroid dehydrogenase locus and adipose tissue distribution phenotypes. A total of 132 unrelated individuals from the Quebec Family Study were followed prospectively for an average period of 11.3 years. The BglII polymorphism in exon 4 of the 3beta-HSD gene was detected by PCR. Body mass, body fat, and regional fat distribution indicators were adjusted for age and age2 within each gender. Associations were assessed in unrelated adults with ANOVA across three genotypes. No association was found for the indicators of body mass, body fat, and regional distribution of adipose tissue measured in 1992. In women, the changes (difference between data collected in 1992 and at entry) in the sum of six skinfolds (p=0.04), abdominal skinfold (p=0.01), and abdominal skinfold adjusted (p=0.03) for the sum of six skinfolds at entry were related to the BglII polymorphism at the 3beta-HSD locus. These relations were not found in men, but they gained less body mass and body fat over the 11.3-year period. This suggests that sequence variation at the 3beta-HSD locus or in neighboring genes on chromosome 1 may contribute to individual differences in body fat content and adipose tissue distribution in adult women, particularly in abdominal adipose tissue deposition as they grow older and gain body fat.

3-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

The pharmacokinetics and tissue distribution of gomphoside in Wistar rats.

The excretion and tissue distribution of [3H]-gomphoside was studied after i.p. and i.v. administration of the cardiac glycoside (1 micrograms/g) to male Wistar rats. Following an intraperitoneal dosage of [3H]-gomphoside, most of the radioactivity (greater than 80%) had been excreted from the body by the end of 48 hours. Biliary excretion played a major role in elimination of [3H]-gomphoside with 90 +/- 15% of radioactivity being collected in 24 hours. Renal excretion formed a minor route of elimination of the cardiac glycoside; only 6 +/- 2% being excreted over 6 days. The distribution of radioactivity to tissues after an intravenous dose was rapid; most of the dose was located in the liver (32%), and the skeletal muscle (31%) 3 minutes after injection. The pharmacokinetics of [3H]-gomphoside could be described by a two-compartment open model with an average elimination half-life of 3.7 hours, and a large volume of distribution (2.3 +/- 0.3 ml/g body weight) characteristic of the commonly used cardiac glycosides (1).

Animals↗

PubMed1989

A minipig model of body adipose tissue distribution.

A relatively increased central (truncal) distribution of body adipose tissue has been associated with increased risk for the development of coronary heart disease in human beings. Animal models available to study this phenomenon have been limited. Validity and reliability studies of B-mode ultrasound for the measurement of subcutaneous adipose tissue thickness in miniature swine were conducted. The results showed that ultrasound measurements of subcutaneous adipose tissue thickness were accurate (+/- 0.1 cm) 95 percent of the time when compared to direct in situ ruler measurements. There was no significant systematic measurement error. Ultrasound measurements were repeatable (+/- 0.2 cm) 95 percent of the time. A computerized tomographic (CT) method to quantitate intra-abdominal adipose tissue was also developed. Serial CT measurement of total cross-sectional, density-contoured adipose tissue area correlated significantly (r = 0.91, P less than 0.01) with total intra-abdominal adipose tissue weight. This model should be useful for comparative study of the association of regional body adipose tissue distribution with the development of atherosclerotic lesions and other coronary heart disease risk factors.

Adipose Tissue↗

PubMed1998

Effect of liposomalization on the antitumor activity, side-effects and tissue distribution of CPT-11.

We have examined the efficacy of liposomalization and polyethyleneglycol (PEG) modification of liposomes on the antitumor activity, side-effects and tissue distribution of irinotecan hydrochloride (CPT-11). PEG-liposome was confirmed to elevate the plasma circulation of CPT-11 and SN-38 (active metabolite) concentrations. The tumor accumulation of CPT-11 and SN-38 was increased by the PEG-modified liposomes. The antitumor activity of CPT-11 increased due to the elevated tumor distribution of CPT-11 and SN-38 levels by the PEG-modified liposomes. In the tumor, CPT-11 was converted to SN-38. Thus, it is considered that passive targeting to the tumor by liposomalization elevated the SN-38 level in the tumor especially and increased the antitumor activity of CPT-11. Furthermore, intestinal disorder, a side toxicity of CPT-11, decreased dependent on the CPT-11 and SN-38 concentrations in the bile by liposomalization. Although the liposomes induce improved tissue distribution of the prodrug, the tissue distribution of active metabolites does not always improve. However, CPT-11-entrapped liposome was useful, as CPT-11 is converted to SN-38 in the tumor. These results suggested that the usefulness of CPT-11 could be extended.

Animals↗

PubMed1976

Phencyclidine: tissue distribution in the rat.

This study was performed to provide knowledge of the tissue distribution of phencyclidine and has demonstrated the lipophilic nature of the drug. The distribution of phencyclidine in blood, brain, and adipose tissue of rats has been determined at various time intervals during a 48-hr period. The affinity of phencyclidine for adipose tissue and the demonstration of the presence of this drug in brain tissue long after it is no longer detectable in blood provides some correlation between the tissue distribution of phencyclidine and its clinical manifestations occuring 24-48 hr after administration.

Adipose Tissue↗

PubMed1996

Pharmacokinetics, tissue distribution, and expression efficiency of plasmid [33P]DNA following intravenous administration of DNA/cationic lipid complexes in mice: use of a novel radionuclide approach.

The pharmacokinetics, tissue distribution, and efficacy of a systemic gene transfer method were examined in male BALB/c mice (6-8 weeks old) using 33P-labeled plasmid DNA for luciferase. The DNA was delivered via tail vein injection in saline ([33P]DNA) or in a cationic lipid formulation ([33P]DNA/lipid). One group of mice received approximately equal to 1-3 microCi (45 micrograms of DNA) of either formulation, and mice were euthanized at 2 and 20 min, and 1 and 24 h postdose (2 mice/time point). Blood and plasma radioactivity were quantified, and whole body autoradiographic (WBAR) images were obtained from 20-microns whole body sections. A tissue distribution (TD) study was conducted in a second group of mice, which received approximately equal to 4-6 microCi (45-60 micrograms of DNA) of [33P]DNA/lipid. Mice were euthanized at 1.5 h (1 mouse; [33P]DNA/lipid) or 24 h (2 mice/ group), and organ radioactivity and luciferase expression were measured in lung, liver, kidney, spleen thymus, and parotid salivary gland by direct quantitation methods. Microautoradiography (MAR) was performed on a third group of mice (n = 2), which received 3 microCi (45 micrograms of DNA) of [33P]DNA/lipid and were euthanized at 24 h postdose. For WBAR, the [33P]DNA/lipid tissue distribution (% dose equiv/g) at 2 min was lung >> liver > spleen (red pulp) > kidney (cortex); at 24 h the ranking was spleen (red pulp) > liver > lung, kidney (cortex). The [33P]DNA organ distribution observed at 2 min was liver >> spleen (red pulp) > lung, blood > kidney (cortex); at 24 h the ranking was liver, spleen (red pulp) > kidney (cortex) > lung, blood. High levels of radioactivity in bone (cortical, marrow, growth plate) in both groups may represent uptake of the 33P-labeled test articles by the cellular component of the bone marrow, particularly macrophages, as well as deposition of [33P]phosphate in the bone matrix following metabolism of the [33P]DNA. In the luciferase component of the study, no expression was observed in the [33P]DNA group at 24 h. The [33P]- DNA/lip group exhibited expression as early as 1.5 h in the lung; at 24 h, expression was seen in all the organs examined. Microautoradiography of 24-h tissue samples revealed radioactivity in hepatic Kupffer cells, reticuloendothelial system cells in the marginal zone of the spleen, and diffusely along alveolar septae with scattered accumulations in alveolar macrophages. The results of the WBAR, TD, MAR, and luciferase assay show that the use of cationic lipids significantly altered the biodistribution and resulting expression of the DNA plasmid. Further, 33P (0.25 MeV beta, half-life = 25 days) was shown to be an excellent radionuclide for quantitative WBA and MAR, providing sharp images with less personal hazard and greater ease of handling than 32P (1.71 MeV beta, half-life = 14.3 days).

Animals↗

PubMed1982

Manipulation of toxicity and tissue distribution of tubercidin in mice by nitrobenzylthioinosine 5'-monophosphate.

The i.v. administration of tubercidin, an analog of adenosine, in a single dose of 45 mg/kg caused death in about 90% of B10D2F1 mice so treated. Serum and urine analysis, as well as histological examination of tissues, related the lethality of tubercidin to hepatic injury, which was markedly reduced when mice were treated with the inhibitor of nucleoside transport, nitrobenzylthioinosine 5'-monophosphate (NBMPR-P), at i.p. doses higher than 10 mg/kg 30 min prior to tubercidin injection. With high NBMPR-P doses (100 mg/kg, i.p.) followed by tubercidin injection (45 mg/kg, i.v.), kidney damage and high mortality occurred. The tissue distribution of 3H following (( G-3H]tubercidin administration paralleled hepatic or renal injury: NBMPR-P treatment decreased the content of tubercidin-derived 3H in liver and increased that in kidney. Furthermore, the half-life of the decline in tubercidin levels in serum during the first minute after[3H]tubercidin administration was longer in NBMPR-P-treated mice (26 sec) than in untreated mice (10 sec), with the result that 3H levels in serum were more than ten times higher in the former than in the latter at an early stage during the distribution of tubercidin. Within 15 min after i.p. administration, the tissue distribution of (( 3H]tubercidin was complete. The i.p. administration of tubercidin caused ascites and the appearance of amylase in the peritoneal fluid evidently because of peritonitis and pancreatic injury. Administration of NBMPR-P by the i.p. route, but not by the i.v. route, prevented these injuries and shifted the LD50 of i.p. injected tubercidin (5 mg/kg) to markedly higher values (a 4-fold increase with NBMPR-P at 100 mg/kg). The protection of mice by NBMPR-P against lethal injuries caused by i.p. injected tubercidin was consistent with the inhibition by NBMPR-P of tubercidin accumulation in mesentery and pancreas. The tissue specificity of the NBMPR-P influence on the tissue distribution of tubercidin may reflect differences in NBMPR-P pharmacokinetics and/or in properties of the nucleoside permeation mechanism among various tissues.

Animals↗

PubMed1984

Tissue distribution of prednisolone in the rabbit.

The tissue distribution and kinetics of prednisolone disposition were examined in the rabbit under steady-state conditions. The steroid was infused to attain a range of plasma (362-4528 ng/ml) and tissue concentrations of pharmacologic interest. Blood components and various tissues were analyzed for prednisolone and its major metabolite, prednisone, by high-performance liquid chromatography. Unbound prednisolone was measured in plasma (percentage of binding = 72-82%) by equilibrium dialysis and tissue binding was calculated from tissue/unbound plasma distribution ratios (Kp) and fractional water content. The small intestine (Kp = 6.65), heart (2.92), kidney (2.91), lung (2.86), skeletal muscle (1.54) and spleen (1.16) exhibited linear Kp values and percentage of tissue binding. Red cell content reflected unbound prednisolone in plasma. Liver uptake (Kp = 0.38-4.47) was nonlinear with apparent tissue binding ranging from less than 59 to 84%. Slight nonlinearity occurred in prednisolone-prednisone interconversion with the liver, kidney and spleen accounting for prednisone formation. Renal clearance of prednisolone was small (6-9% of total clearance), but appreciable steroid concentrations in the bile and small intestine indicate probable enterohepatic cycling. The steady-state total and unbound plasma clearances of prednisolone were similar to those from single-dose studies. Prednisolone-prednisone interconversion and enterohepatic cycling affect the steady-state volume of distribution generated from single-dose studies as the body content/plasma concentration measure of steady-state volume of distribution is about one-half of that estimated conventionally from plasma disposition curves.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Pharmacokinetic profile of recombinant human (rh) inhibin A and activin A in the immature rat. II. Tissue distribution of [125I]rh-inhibin A and [125I]rh-activin A in immature female and male rats.

The tissue distribution of recombinant human inhibin A (rh-inhibin A) and rh-activin A was determined in immature female Sprague Dawley-derived rats after iv administration of radiolabeled proteins. [125I]rh-Inhibin A and [125I]rh-activin A diverge in their distribution to tissues of the immature female rat as examined histologically (whole body autoradiography and thin section analysis) and by computing the percent dose and tissue to blood ratios for individual tissues. [125I]rh-inhibin A accumulated in the spleen, adrenal, bone marrow, and ovary after iv injection. Iodinated rh-inhibin A was also found in the anterior and posterior pituitary. [125I]rh-activin A was found in the ovary and pituitary after iv injection. Little specific binding was found in the spleen or adrenal. The bone marrow accumulated some [125I]rh-activin A which was competed by rh-activin A. The primary route of excretion for radioactivity was the kidney, with the label appearing in the bladder by 10 min after iv injection. Not only do rh-inhibin A and rh-activin A have different pharmacokinetics, but fewer tissues accumulate radioactive rh-activin A than rh-inhibin A.

Activins↗

PubMed1982

Whole-body retention and tissue distribution of 60Co in rats after oral administration of freshwater fish contaminated with 60Co.

The purpose of this report is to compare the whole-body retention and tissue distribution in rats of 60Co administered by gavage as inorganic 60CoCl2 or in a form incorporated into freshwater fish. Orizias latipes were placed in vessels containing 21. of tap water with radioactive cobalt. Periodically thereafter the fish were sacrificed, homogenized, and administered to rats via a stomach tube. Control groups of rats were given the radionuclide alone or together with a homogenate of nonradioactive fish. The whole-body retention and tissue distribution of the radionuclide were determined with an Armac counter. The results revealed that rats gavaged with 60Co incorporated into the fish retained much more 60Co than control rats. This trend was notable in rats given fish kept in radioactive solution for longer periods. Marked differences in tissue distribution of 60Co were also observed between rats given 60Co incorporated into fish and control rats.

Animals↗

PubMed1980

Tissue distribution and elimination of 2,8-dihydromirex in the rat.

The tissue distribution and elimination kinetics of 14C-labeled dihydromirex were investigated in the rat. Dihydromirex was distributed in all tissues examined after iv or oral administration; the highest concentrations were found in the fat, liver, and skin. The pattern of distribution was similar to that of photomirex and mirex. Elimination of dihydromirex from the blood after an iv dose was expressed by a four-compartment model, whereas fecal excretion was represented by a biphasic curve. Excretion of dihydromirex occurred predominantly in the feces; only minute amounts were found in the urine and bile. Dihydromirex constituted 90-100% of the total radioactivity in tissues and feces. No metabolite was detected.

Adipose Tissue↗

PubMed1995

Tissue distribution and deposition of clofazimine in rat following subchronic treatment with or without rifampicin.

Tissue distribution and deposition characteristics of clofazimine (CAS 2030-63-9), an antileprotic drug in rats have been investigated following controlled sub-chronic administration (p.o.) for a period of 1-2 months. The drug was administered alone at a dose of 20 mg/kg body weight and in combination with rifampicin (CAS 13292-46-1) (20 mg/kg p.o.). Various tissues (liver, lung, spleen, small intestine, brain, heart, kidney, skin, stomach and subcutaneous fat) were analyzed for clofazimine in all the treated groups. High levels (range 0.9-3.6 mg/g of wet tissue) were observed in tissues having reticuloendothelial components. In other tissues the levels were relatively lower (range 3-114 micrograms/g of wet tissue). Histopathological studies revealed that clofazimine is deposited in many tissues in the form of reddish-orange crystals. Concomitant treatment with rifampicin did not significantly alter tissue distribution or deposition profile of clofazimine nor did it influence the histopathology.

Animals↗

PubMed1986

The use of monoclonal antibodies for the species and tissues distribution of phospholamban.

Monoclonal antibodies have been raised against canine phospholamban. Two antibodies have been used in the study of phospholamban distribution in tissues, and in different animal species. The antibodies recognized the three different forms of phospholamban: non-phosphorylated, phosphorylated, and dissociated forms. A survey of nine rabbit tissues revealed that phospholamban is a cardiac muscle specific protein. Phospholamban from different mammalian hearts were found to be identical with respect to molecular weight and antigenicity.

Animals↗