LIVER DISTRIBUTION OF COPPER AND 99Mo IN SHEEP FOLLOWING INTRAVENOUS ADMINISTRATION OF COPPER SULFATE AND [99Mo]-TETRATHIOMOLYBDATE

1986 ◽  
Vol 66 (2) ◽  
pp. 563-565
Author(s):  
C. A. KELLKHER ◽  
M. IVAN
Keyword(s):  
Key Words ◽  
Copper Sulfate ◽  
Intravenous Administration ◽  
Subcellular Distribution ◽  
Subcellular Fractionation ◽  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Lysosomal Fraction ◽  
Liver Homogenates

The effect of a single intravenous dose of 0, 50 or 100 g molybdenum (Mo) as [99Mo] labelled sodium tetrathiomolybdate (Na2MoS4) on the subcellular distribution of copper (Cu) in the liver was studied in three groups of four sheep. The sheep received a 35-mg intravenous dose of Cu 20 h prior, and were killed 24 h after the dosing with Mo. Subcellular fractionation of liver homogenates revealed that [Formula: see text] may react with Cu in the nuclear (lysosomal) fraction. Key words: Sheep, copper, molybdenum, tetrathiomolybdate, liver fractions

scholarly journals Pharmacokinetics of Intermittent Intravenous Cefazolin and Tobramycin in Patients Treated with Automated Peritoneal Dialysis

2000 ◽  
Vol 11 (7) ◽  
pp. 1310-1316
Author(s):  
HAROLD J. MANLEY ◽  
GEORGE R. BAILIE ◽  
REGINALD FRYE ◽  
LORRAINE D. HESS ◽  
M. DONALD MCGOLDRICK
Keyword(s):  
Peritoneal Dialysis ◽  
Intravenous Administration ◽  
Intraperitoneal Administration ◽  
Intravenous Dose ◽  
Urine Samples ◽  
Pharmacokinetic Parameters ◽  
Single Intravenous Dose ◽  
Automated Peritoneal Dialysis ◽  
Minimum Inhibitory Concentrations ◽  
Monoexponential Model

Abstract. There is increasing use of intermittent dosing of antibiotics to treat peritoneal dialysis (PD)-related peritonitis. The disposition of intravenous cefazolin and tobramycin was studied in automated PD (APD) patients. Ten patients were recruited and received a single intravenous dose of cefazolin (15 mg/kg) and tobramycin (0.6 mg/kg). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 to 3 (on cycler), and at the end of dwells 4 to 5 (off cycler) for a 24-h period. Baseline and 24-h urine samples were collected. Pharmacokinetic parameters were calculated using a monoexponential model. Cefazolin and tobramycin half-lives were markedly different on cycler than off cycler (cefazolin on cycler : 10.67 ± 4.66 h ; cefazolin off cycler : 23.09 ± 5.6 h ; P = 0.001 ; tobramycin on cycler : 14.27 ± 4.53 h ; tobramycin off cycler : 68.5 ± 26.47 h ; P < 0.001). Mean serum and dialysate concentrations were above minimum inhibitory concentrations of susceptible organisms throughout the 24-h period for both drugs with intravenous administration. A model was developed to examine serum and dialysate concentrations after intermittent intraperitoneal administration of 15 mg/kg cefazolin and 0.6 mg/kg tobramycin. Model-predicted intraperitoneal cefazolin provides adequate serum and dialysate concentrations for 24 h. Intermittent intraperitoneal tobramycin doses must be 1.5 mg/kg for one exchange during the first day and then given as 0.5 mg/kg thereafter. It is concluded that the current empiric dosing recommendations for PD-related peritonitis may be adequate for cefazolin (15 to 20 mg/kg) ; however, tobramycin doses must be changed to 1.5 mg/kg intraperitoneally on day 1, then to 0.5 mg/kg intraperitoneally thereafter in APD patients.

scholarly journals Pharmacokinetics, Toxicities, and Efficacies of Sodium Stibogluconate Formulations after Intravenous Administration in Animals

2003 ◽  
Vol 47 (9) ◽  
pp. 2781-2787 ◽  
Author(s):  
J. Nieto ◽  
J. Alvar ◽  
A. B. Mullen ◽  
K. C. Carter ◽  
C. Rodríguez ◽  
...  
Keyword(s):  
Intravenous Administration ◽  
Hepatic Dysfunction ◽  
Volume Of Distribution ◽  
Free Drug ◽  
Intravenous Dose ◽  
Sodium Stibogluconate ◽  
Single Intravenous Dose ◽  
Short Term ◽  
Elimination Half ◽  
Healthy Dogs

ABSTRACT The pharmacokinetics and toxicities of free sodium stibogluconate (SSG) and two vesicular formulations of this drug (a nonionic surfactant vesicular formulation of SSG [SSG-NIV] and SSG-NIV-dextran) were determined after treatment with a single intravenous dose in healthy dogs and were related to their antileishmanial efficacies in mice. Analysis of the curves of the concentrations in plasma after intravenous administration of SSG and SSG-NIV in dogs showed that both formulations produced similar antimony (Sb) pharmacokinetics. In contrast, treatment with SSG-NIV-dextran significantly modified the pharmacokinetics of the drug. The elimination half-life was four times longer (280 min) than that observed after administration of SSG (71 min) (P = 0.01), and the volume of distribution at steady state (V SS) was also increased (V SS for SSG, 0.21 liters/kg; V SS for SSG-NIV-dextran, 0.34 liters/kg [P = 0.02]), thus indicating that drug encapsulation favors the distribution of Sb into organs and increases its residence time in tissues. This would explain the superior antileishmanial efficacy of this formulation compared to those of the free drug in mice. No signs of toxicity were found in dogs after SSG and SSG-NIV administration. However, SSG-NIV-dextran treatment was associated with short-term toxicity, demonstrated by the development of chills and diarrhea, which cleared by 24 h postdosing, and hepatic dysfunction at 24 h postdosing (P < 0.05). The levels of all the biochemical parameters had returned to normal at 1 month postdosing. No signs of toxicity were observed in mice treated with all three formulations.

scholarly journals The mechanism of hepatic iron uptake from native and denatured transferrin and its subcellular metabolism in the liver cell

1979 ◽  
Vol 182 (1) ◽  
pp. 117-125 ◽  
Author(s):  
J P Milsom ◽  
R G Batey
Keyword(s):  
Rat Liver ◽  
Liver Cell ◽  
Iron Uptake ◽  
Subcellular Fractionation ◽  
Hepatic Iron ◽  
Lysosomal Fraction ◽  
Uptake Process ◽  
Liver Homogenates ◽  
Uptake And Metabolism

Hepatic iron uptake and metabolism were studied by subcellular fractionation of rat liver homogenates after injection of rats with a purified preparation of either native or denatured rat transferrin labelled with 125I and 59Fe. (1) With native transferrin, hepatic 125I content was maximal 5 min after injection and then fell. Hepatic 59Fe content reached maximum by 16 h after injection and remained constant for 14 days. Neither label appeared in the mitochondrial or lysosomal fractions. 59Fe appeared first in the supernatant and, with time, was detectable as ferritin in fractions sedimented with increasingly lower g forces. (2) With denatured transferrin, hepatic content of both 125I and 59Fe reached maximum by 30 min. Both appeared initially in the lysosomal fraction. With time, they passed into the supernatant and 59Fe became incorporated into ferritin. The study suggests that hepatic iron uptake from native transferrin does not involve endocytosis. However, endocytosis of denatured transferrin does occur. After the uptake process, iron is gradually incorporated into ferritin molecules, which subsequently polymerize; there is no incorporation into other structures over 14 days.

Cytopathology of Cardiac Tissue from Daunomycin-Treated Mice

1971 ◽  
Vol 29 ◽  
pp. 550-551
Author(s):  
Robert H. Liss ◽  
Frances A. Cotton
Keyword(s):  
Cardiac Tissue ◽  
Cardiac Toxicity ◽  
Drug Distribution ◽  
Personal Communication ◽  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Physiologic Saline ◽  
Histopathologic Changes ◽  
Distribution Studies ◽  
Lung And Kidney

Daunomycin, an antibiotic used in the clinical management of acute leukemia, produces a delayed, lethal cardiac toxicity. The lethality is dose and schedule dependent; histopathologic changes induced by the drug have been described in heart, lung, and kidney from hamsters in both single and multiple dose studies. Mice given a single intravenous dose of daunomycin (10 mg/kg) die 6-7 days later. Drug distribution studies indicate that the rodents excrete most of a single dose of the drug as daunomycin and metabolite within 48 hours after dosage (M. A. Asbell, personal communication).Myocardium from the ventricles of 6 moribund BDF1 mice which had received a single intravenous dose of daunomycin (10 mg/kg), and from controls dosed with physiologic saline, was fixed in glutaraldehyde and prepared for electron microscopy.

scholarly journals Hepatic endosome fractions contain an ATP-driven proton pump

1985 ◽  
Vol 225 (1) ◽  
pp. 51-58 ◽  
Author(s):  
T Saermark ◽  
N Flint ◽  
W H Evans
Keyword(s):  
Endoplasmic Reticulum ◽  
Golgi Apparatus ◽  
Atpase Activity ◽  
Proton Pump ◽  
Subcellular Distribution ◽  
Plasma Membranes ◽  
Specific Activity ◽  
Ph Gradients ◽  
Subcellular Organelle ◽  
Liver Homogenates

Endosome fractions were isolated from rat liver homogenates on the basis of the subcellular distribution of circulating ligands, e.g. 125I-asialotransferrin internalized by hepatocytes by a receptor-mediated process. The distribution of endocytosed 125I-asialotransferrin 1-2 min and 15 min after uptake by liver and a monensin-activated Mg2+-dependent ATPase activity coincided on linear gradients of sucrose and Nycodenz. The monensin-activated Mg2+-ATPase was enriched relative to the liver homogenates up to 60-fold in specific activity in the endosome fractions. Contamination of the endosome fractions by lysosomes, endoplasmic reticulum, mitochondria, plasma membranes and Golgi-apparatus components was low. By use of 9-aminoacridine, a probe for pH gradients, the endosome vesicles were shown to acidify on addition of ATP. Acidification was reversed by addition of monensin. The results indicate that endosome fractions contain an ATP-driven proton pump. The ionophore-activated Mg2+-ATPase in combination with the presence of undegraded ligands in the endosome fractions emerge as linked markers for this new subcellular organelle.

scholarly journals Effect of polyaspartic acid on pharmacokinetics of gentamicin after single intravenous dose in the dog.

1996 ◽  
Vol 40 (5) ◽  
pp. 1237-1241 ◽  
Author(s):  
T Whittem ◽  
K Parton ◽  
K Turner
Keyword(s):  
Aspartic Acid ◽  
Elimination Rate ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Peripheral Compartment ◽  
Single Intravenous Dose ◽  
Polyaspartic Acid ◽  
Peripheral Tissues

The effects of poly-L-aspartic acid on the pharmacokinetics of gentamicin were examined by using a randomized crossover trial design with the dog. When analyzed according to a three-compartment open model, poly-L-aspartic acid reduced some first-order rate equation constants (A3, lambda 1, and lambda 3), the deep peripheral compartment exit microconstant (k31), the elimination rate constant (k(el)), and the area under the concentration-time curve from 0 to 480 h (AUC0-480) (0.21-, 0.60-, 0.26-, 0.27-, 0.72-, and 0.76-fold, respectively; P < 0.05) but increased the volume of distribution at steady state (Vss), the volume of distribution calculated by the area method (V(area)), the apparent volume of the peripheral compartment (Vp), and all mean time parameters. These results suggested that poly-L-aspartic acid increased the distribution of gentamicin to or binding within the deep peripheral compartment and that poly-L-aspartic acid may have delayed gentamicin transit through the peripheral tissues. In contrast, poly-L-aspartic acid did not alter pharmacokinetic parameters relevant to the central or shallow peripheral compartments to a clinically significant extent. Although gentamicin's pharmacokinetic parameters of relevance to therapeutic drug monitoring were not directly altered, this study has provided pharmacokinetic evidence that poly-L-aspartic acid alters the peripheral distribution of gentamicin. This pharmacokinetic interaction occurred after a single intravenous dose of each drug. Therefore, this interaction should be investigated further, before polyaspartic acid can be considered for use as a clinical nephroprotectant.

Letters to the Editor

PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 601-602
Author(s):  
M. Spino ◽  
J. J. Thiessen ◽  
A. Isles ◽  
H. Levison ◽  
S. M. MacLeod
Keyword(s):  
Clinical Application ◽  
Drug Concentration ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Intravenous Dose ◽  
Single Intravenous Dose ◽  
Letters To The Editor ◽  
Potential Clinical Application ◽  
Apparent Volume Of Distribution

We found the report by Feldman et al1 interesting with potential clinical application. However, we would like to point out an error in their determination of the apparent volume of distribution (V) and comment on both their methodology and results. They state that V was calculated by dividing the dose of the drug by the extrapolated y intercept for drug concentration at time 0. This method is correct for a drug which exhibits monoexponential elimination following a single intravenous dose.

A double-blind trial of a single intravenous dose of metronidazole as prophylaxis against wound infection following appendicectomy

1979 ◽  
Vol 66 (6) ◽  
pp. 428-429 ◽  
Author(s):  
M. J. Greenall ◽  
A. Bakran ◽  
I. R. Pickford ◽  
J. A. Bradley ◽  
A. Halsall ◽  
...  
Keyword(s):  
Wound Infection ◽  
Intravenous Dose ◽  
Double Blind Trial ◽  
Single Intravenous Dose ◽  
Double Blind ◽  
Blind Trial
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