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Biomedical subjects

I Janku

Publications and source records attributed to I Janku.

17 recordsLinked to original sources
PubMed1998

Disposition and tissue distribution of boron after infusion of borocaptate sodium in patients with malignant brain tumors.

PURPOSE: In the frame of the Czech boron neutron capture therapy (BNCT) project, a clinical Phase I study of borocaptate sodium [Na2B12H11SH (BSH)] as the boron-10 delivery agent was performed to obtain data on disposition and tissue distribution of boron after an infusion of this compound, as well as to establish an optimal protocol for BNCT of malignant cerebral tumors. METHODS AND MATERIALS: The kinetics of boron disposition after an infusion of borocaptate sodium (25 mg/kg body wt over the period of 1 h) was studied in a group of 10 patients with astrocytoma or glioblastoma of cerebral hemispheres using a modification of the Soloway-Messer colorimetric method. The boron content of tissues (tumor, healthy brain, dura mater, muscle, skin, and cranial bone) removed during the operation performed with latencies varying between 3 and 18 h was investigated by atomic emission spectrometry. RESULTS: Compartmental analysis of boron blood concentrations has shown that in the majority of patients (four males and three females), the concentration decline can be adequately described by a two-compartment pharmacokinetic model (i.e., by a biexponential relationship). The calculated half-lives of the initial (fast) phase of the concentration decline varied between 0.85 and 3.65 h, whereas the half-life values for the terminal (slow) phase ranged between 22.2 and 111.8 h. However, in the remaining three patients (all females), the goodness of fit of the boron concentration data was significantly better when a pharmacokinetic model with three compartments was assumed. In these patients, therefore, an additional ultrafast phase with a half-life varying between 17 and 37 min was detected in the beginning of the boron blood concentration decline. On the other hand, in one of these patients, the half-life of the terminal phase was found to be 415 h (i.e., more than 17 days). Such a long persistence in the body is explained by the very high value of the total distribution volume, indicating extensive binding of BSH in peripheral tissues. Another reason may be enterohepatic recycling of BSH. CONCLUSION: Tumor-to-blood ratios higher than 1.5, which are necessary for an effective outcome of BNCT, can be obtained only if the time interval elapsing between the onset of surgery and termination of BSH infusion is at least 12 h.

Adult↗
PubMed1997

The diuretic effect of borocaptate sodium in rats and in patients with brain tumors.

Kidney function changes after single-dose administration of borocaptate sodium were studied in rats and in patients with brain tumors. Changes of glomerular filtration rate (GFR) measured as 14C-inulin clearance and urine flow rate (UFR) after a slow intravenous injection of BSH (25 and 50 mg/kg b.w., respectively) were investigated in rats under pentobarbital anesthesia. The effect of BSH has been compared with that of its disulfide (BSSB) which is spontaneously generated by oxidation of BSH during storage. It was found that BSH decreases GFR in relation to dose and, in the same way, causes a temporary increase of UFR. On the other hand, BSSB (50 mg/kg) induced a large reversible decrease of GFR as well as a decrease of urine excretion. Measurements of GFR (inulin clearance), renal plasma flow (PAH clearance) and urine excretion were taken in a group of patients with brain tumors in which boron disposition after an infusion of BSH (25 mg/kg b.w. over 1 h) had been studied. An increase in urine production was the dominant effect (up to 200% of the initial value), with the alterations of GFR and RPF being of minor significance except in one patient with a GFR reduction up to almost 50% the original value. Kidney function changes after BSH or BSSB administration are supposedly related to the high retention of BSH in kidney.

Animals↗
PubMed1994

The in vitro effect of sodium mercaptoundecahydrododecaborate (borocaptate) on sulfhydryl groups of different rat tissues.

The effect of borocaptate on structural protein sulfhydryl (SH) groups of different organs and kidney subcellular fractions was studied in vitro. It was shown that the binding capacity of borocaptate is not the same for different tissues and subcellular fractions. The highest binding capacity was in the liver, while kidney and brain values were significantly lower. Therefore, it appears that the same concentration of borocaptate may have different effects in various organs.

Animals↗
PubMed1990

[Kemantane pharmacokinetics in rats].

Pharmacokinetics of novel immunostimulating drug kamantane was studied by using gas-liquid chromatography in experiments on rats. It was found that kemantane biotransformed rapidly after oral administration with the forming of active metabolite. Kemantane and its metabolites are distributed rapidly from the blood to organs. The drug is eliminated from the organism of rats as metabolite.

Adamantane↗
PubMed1990

Effect of schistosomiasis infection on the clearance of phenazone in mice.

The disposition phenazone (antipyrine) was used to study the effect of Schistosoma mansoni infection on the activity of drug metabolizing enzymes in mice. Plasma elimination rate constant (Ke), elimination half-life (t1/2e), clearance (CL) and apparent volume of distribution (Vd) were estimated 8 and 12 weeks after infection of mice with 80 S. mansoni cercariae. Liver and kidney function tests were performed simultaneously. Infection increased the levels of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), lactic dehydrogenase (LDH), alkaline phosphatase (AP) and total proteins 8 and 12 weeks post infection. At the same time a decrease was recorded in the total cholesterol level. Moreover infection with S. mansoni produced a decrease in phenazone clearance with an increase in the area under the curve (AUC) of the drug 8 and 12 weeks post infection. Elimination half-lives were 57.92 +/- 14.10 and 72.72 +/- 4.14 min 8 and 12 weeks after infection, respectively, compared to 19.29 +/- 3.30 and 26.14 +/- 5.31 min in corresponding controls. No statistically significant change was recorded in the volume of distribution of phenazone in the groups studied. In addition no significant correlation was found between parameters of phenazone disposition and the enzyme levels studied 8 and 12 weeks after infection.

Animals↗
PubMed1988

The effect of guaiphenesin on absorption and bioavailability of paracetamol from composite analgesic preparations.

Using a one compartment pharmacokinetic model with constant rate of availability for absorption, the disposition of paracetamol was compared after administration of Paralen (paracetamol 500 mg in one tablet) with data obtained after administration of two composite analgesic preparations: Guajanal (paracetamol 500 mg, guaiphenesin 200 mg) and Ataralgin (paracetamol 500 mg, guaiphenesin 130 mg, caffeine 70 mg). The combination of paracetamol with guaiphenesin significantly increased the rate of paracetamol absorption availability, most probably by accelerating its transfer from the stomach to the small intestine. The combination with guaiphenesin and caffeine slightly reduced the rate of paracetamol absorption availability but the difference was not statistically significant. The relative bioavailability of paracetamol from the composite analgesic preparations, however, did not show a statistically significant difference as compared to the preparation where paracetamol was present as a single component.

Acetaminophen↗
PubMed1985

The effect of adjuvant-induced arthritis on rat liver microsomal phospholipid metabolism.

Rats given a single subdermal injection into the left hind paw of 0.5 mg Mycobacterium tuberculosis suspended in 0.1 ml of mineral oil, after several days of latency, developed arthritis accompanied by depression in liver microsomal phosphatidylcholine and phosphatidylethanolamine synthesis at 7, 14 and 21 days. The depression of liver microsomal phosphatidylcholine and phosphatidylethanolamine concentrations of experimental animals was accompanied by decreased incorporation of radioactive palmitate into both phospholipids. Nevertheless, the biosynthesis of phosphatidylcholine via the methylation pathway was unaffected. These observations suggest that adjuvant arthritis affects quantitatively the phospholipid composition of the liver endoplasmic reticulum, which consequently may lead to impairment of the microsomal drug-metabolizing enzyme system.

Animals↗
PubMed1982

[Simulation of kinetics of phenazepam and its metabolite 3-hydroxyphenazepam in cat blood].

The pharmacokinetics of the tranquilizer phenazepam and its high-active metabolite 3-hydroxyphenazepam in the cat blood was studied in experiments using gas liquid chromatography and mathematic simulation. The experimental findings were computer-processed. An appreciable quantity of 3-hydroxyphenazepam was found in the blood in addition to the unchanged drug at any times after oral administration of phenazepam (2 mg/kg). Joint modelling of the kinetics of phenazepam and 2-hydroxyphenazepam within the same metabolic model allowed calculating the kinetic parameters of both the compounds. The elimination constant of the metabolite in cats was found to be twice as high on the average as compared to that of the unchanged drug.

Animals↗
PubMedDate not supplied

Effects of potassium ethylxanthogenate and 2,3-dimercaptopropane sulphonate sodium on the pentobarbital pharmacokinetics and metabolism in male mice.

The effects of potassium ethylxanthogenate (PEX) and 2,3-Dimercaptopropane sulphonate sodium (Unithiol) on the pentobarbital (40 mg/kg, body weight i.v.) (PB) sleeping time, pharmacokinetics, and metabolism, were studied in comparative experiments on male albino mice. It was established that the pretreatment of animals with PEX (80 mg/kg of body weight s.c.) potentiated the PB sleeping time. Unithiol in an equimolar dose (105.2 mg/kg of body weight s.c.) had no effect. The pharmacokinetics of PB could be fitted to be a biexponential equation of the type Cp(t) = A.e-alpha t + B.e-beta t. PEX caused an almost two-fold decrease in the elimination rate constant of plasma PB, which led to a higher half-time and a lower total clearance compared with the controls. The curve for the plasma PB metabolites in the PEX-pretreated mice was significantly lower than of the controls. A higher PB level and decreased rate of elimination in PEX-pretreated animals was observed also in the: liver, lungs, kidney, and brain. A conclusion was drawn that the potentiating effect of PEX on the PB sleeping time is mainly due to inhibition of PB liver metabolism. It was suggested that the differences in the biological effects of the two thiol compounds are due to the differences in their chemical structures: PEX possesses a C = S group but Unithiol lacks this group.

Animals↗
PubMedDate not supplied

Functional and non-functional liver blood flow in patients with liver cirrhosis measured by indocyanine green.

Indocyanine green administration was used in a group of ten patients with liver cirrhosis with portal hypertension to estimate hepatic extraction, liver blood flow and the degree of blood shunting. Extraction coefficients obtained by the hepatic catheterization were well correlated with the pharmacokinetic method. Values of the total liver blood flow measured by the classical method based on Fick's principle were always higher than those evaluated by the pharmacokinetic analysis estimating the functional liver blood flow only. Estimates of the degree of shunting varied between 32.0-78.9% of the total liver blood flow. A statistically significant correlation (r = 0.79) was found between the percentage of the functional fraction of the total liver blood flow and albuminemia. It is suggested that in liver cirrhosis with portal hypertension the reduction of the functional fraction of total liver blood flow is combined with partial impairment of hepatic cell metabolism in the remaining functional areas of the liver. In such a case neither the "intact" nor the "sick hepatocyte" hypotheses are appropriate in their strict sense for the interpretation of the findings.

Humans↗