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Biomedical subjects

B Fichtl

Publications and source records attributed to B Fichtl.

49 records · Page 3Linked to original sources
PubMed1982

Effects of dietary paraffin, squalane and sucrose polyester on residue disposition and elimination of hexachlorobenzene in rats.

Previous studies have shown addition of light liquid paraffin to enhance the elimination of organochlorine xenobiotics. In the present study the effect of paraffin on the elimination of [14C]hexachlorobenzene (HCB) was compared with the effect of possible alternative compounds, squalane and sucrose polyester (SPE). Four groups of 7 rats were fed a diet containing 1.5 ppm [14C]HCB for 4 days followed by 10 days on HCB-free diet. Thereafter one group (control) remained on this diet whereas the other 3 groups received a diet supplemented with 8% (w/w) paraffin, squalane or SPE, respectively. Radioactivity in urine and faeces was measured daily and at the end of the experiment in samples of abdominal fat, muscle, liver, kidney and blood. Dietary treatment with either paraffin, squalane or SPE markedly enhanced faecal excretion of [14C]HCB, whereas urinary excretion was not affected. Both the time course as well as the extent of faecal [14C]HCB elimination were similar in the treated groups. After 3 weeks of treatment the amount of [14C]HCB excreted with faeces was about three times higher in treated animals than in controls. The half-life (t1/2) of [14C]HCB elimination from the body was markedly decreased in treated animals (mean 34--38 days) compared to controls (110 days). [14C]HCB concentrations in some major tissues were significantly reduced to the same extent by all three dietary regimens. Thus squalane and SPE are as effective as paraffin in removing HCB from contaminated animals.

Adipose Tissue↗
PubMed1982

Quinidine-digoxin interaction: evidence for involvement of an extrarenal mechanism.

The influence of quinidine 750mg per day for one week on serum digoxin concentration (SDC) was evaluated in digitalized anuric patients on chronic haemodialysis. During quinidine administration the SDC increased markedly, from 0.84 +/- 0.37 to 1.58 +/- 0.72 ng/ml (p less than 0.01), a comparable effect ot that reported previously in patients with normal renal function. Neither in vitro nor in vivo did quinidine alter the serum protein binding of digoxin. The increase in SDC in anuric patients indicates a decrease in the extrarenal clearance of digoxin, which means that mechanisms other than of renal origin are also involved in the interaction of quinidine and digoxin. There was great interindividual variability in the extent of the quinidine-induced rise in SDC. Regardless of the state of renal function, careful monitoring of digitalized patients seems mandatory once quinidine treatment is initiated.

Anuria↗
PubMed1980

Central cardiovascular effects of nylidrin (buphenine).

The injection of small doses of nylidrin into the vertebral artery lowered blood pressure in chloralose-anesthetized cats. Cerebroventricular perfusion of nylidrin also decreased blood pressure and inhibited or modified cardiovascular reflexes. There was inhibition of the reflex bradycardia evoked by i.v. noradrenaline or angiotensin. Likewise the pressure increase due to bilateral carotid occlusion was diminished. The blood pressure decrease elicited by stimulation of the central stump of a cut vagus nerve was inhibited or reversed. The pattern of central cardiovascular effects of nylidrin seemed not compatible with its well known beta-sympathomimetic properties. Indirect evidence points to an interasction with central alpha-receptors.

Adrenergic beta-Antagonists↗
PubMed1980

Binding of drugs to muscle tissue: dependence on drug concentration and lipid content of tissue.

For a series of 16 drugs the extent of binding to homogenized rabbit skeletal muscle was determined by means of ultrafiltration. The percent bound of basic drugs was essentially constant over a 100- to 1000-fold concentration range, i.e., binding was linear. Among weak organic acids the fraction bound decreased with increasing drug concentration for furosemide, warfarin, phenylbutazone, salicyclic acid and sulfonamides. Fitting of the binding data by Langmuir isotherms appeared to be inappropriate for several reasons. A simple power function (Freundlich isotherm) was found to satisfactorily represent the experimental data. Drug binding properties of muscle homogenate were altered following extraction of lipids with acetone. Lipid-depleted muscle tissue exhibited a decrease in binding of chlorpromazine and propranolol, whereas binding of imipramine was unchanged. Binding of phenytoin, warfarin and sulfadimethoxine was enhanced in lipid-depleted muscle. The results suggest that binding of drugs to muscle tissue cannot solely be explained in terms of partitioning into lipids.

Animals↗
PubMed1978

Binding of drugs to human muscle.

Binding of 22 drugs to human muscle tissue has been determined by ultrafiltration. All drugs tested were bound, the bound fraction ranging from 13% (aminophenazone) to greater than 98% (desipramine). Both linear and nonlinear binding was observed. For chemically related substances, binding to muscle tissue correlated with plasma binding and lipid solubility. There were significant differences in binding to muscle from different individuals. With respect to pharmacokinetics of drugs, it is suggested that binding to muscle tissue may be at least as important as plasma binding.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Interrelation between plasma protein binding, rate of injection and the anaesthetic effect of thiopental.

1. Following thiopental injection to rabbits in doses of 5 mg kg-1 intravenously (i.v.) the sleeping time lasted longer after injection by bolus than after administration made more slowly over 30 or 60s, respectively. 2. Peak concentration in the blood of the animals after bolus injection was about four time higher than after slow injection. 3. The determination of protein binding showed that the unbound fraction of thiopental at the high concentration following bolus injection is almost doubled compared with the unbound concentration following the slow injections. Therefore it is concluded that this contributes to an increased concentration of thiopental in the brain during the initial phase of distribution thus extending the sleeping time. 4. The results from experiments using a distribution model give additional evidence supporting this conception.

Anesthesia, Intravenous↗
PubMedDate not supplied

Pharmacokinetics of 14C-DMPS (sodium-1,3 14C-2,3-dimercaptopropane-1-sulphonate) in beagle dogs.

The pharmacokinetics of labelled DMPS (sodium-1,3 14C-2,3-dimercaptopropane-1-sulphonate) have been studied in four beagle dogs following bolus intravenous injection (65.7 mumol kg-1) and oral administration (197 mumol kg-1). Following intravenous injection the main kinetic parameters were t 1/2 = 43 min, V beta = 160 ml kg-1, and plasma clearance Clp = 2.6 ml min-1 kg-1. Following oral administration 14C-DMPS is rapidly absorbed with peak concentrations (478 +/- 25 mumol l-1) measured after 30-45 min. About 60 per cent of the oral dose was absorbed. Estimates of t 1/2, V beta, and Clp after oral administration were in close agreement with the values obtained in the intravenous study. 14C-DMPS is eliminated from the body by the kidneys. About 70 per cent of 14C-DMPS in dog plasma are bound to proteins. Binding is even higher in plasma from rat and man.

Administration, Oral↗
PubMedDate not supplied

Effect of quinidine on the intestinal secretion of digoxin in guinea pigs.

Following i.v. injection of digoxin (10 micrograms kg-1) the ratio between digoxin concentrations in the lumen of jejunal loops perfused in situ and in plasma (L/P) of guinea pigs increased linearly with time. After 3 h, L/P was 8.7, indicating net secretion of digoxin against a concentration gradient. In quinidine treated animals (100 mg kg-1 p.o., 2 h before experiment) both the L/P ratio (5.7; p less than 0.01) and the digoxin content of jejunal tissue (-32 per cent; p less than 0.01) were markedly reduced. It is suggested that quinidine reduces the extrarenal clearance of digoxin at least in part by inhibiting the intestinal secretion of this glycoside.

Animals↗
PubMedDate not supplied

Prediction of drug distribution in vivo on the basis of in vitro binding data.

For 11 drugs it was investigated whether tissue distribution in vivo can be predicted by use of binding data obtained in vitro. The selection of drugs represented a broad spectrum of physicochemical and pharmacokinetic properties thought to be important for distribution of drugs in vivo. The extent of binding to plasma and to tissue-homogenates of rabbits was determined in vitro. The drug concentrations in plasma, liver, lungs, kidneys, and skeletal muscle of rabbits were determined in vivo after i.v. administration of the drug. The tissue-plasma partition ratios measured in vivo were compared with the theoretical tissue-plasma partition ratios calculated from the in vitro binding data. For all drugs investigated the muscle-plasma partition ratio could be reasonably well predicted by the in vitro binding data. In liver, lungs, and kidneys good agreement was found between measured and predicted tissue-plasma ratio for anionic drugs; marked differences, however, were observed between measured and predicted tissue-plasma ratios of lipophilic cationic drugs. A significant correlation was found between binding of drugs to muscle tissue in vitro and the volume of distribution of the unbound drug (Vf), opening the possibility to approximate Vf from in vitro binding studies with rabbit muscle tissue.

Animals↗
PubMedDate not supplied

Binding of non-steroid anti-inflammatory drugs and warfarin to liver tissue of rabbits in vitro.

Liver slices (10mm 0.1mm thickness) were incubated at 37 degrees C in drug solutions up to 360 min. The drugs were dissolved in Ringer solution of pH 7.0. After 60, 180, 240 and 360 min each drug concentration was determined in the incubation fluid. For all drugs tested equilibrium was obtained after 240 min. The amount of drug taken up by the slices was calculated from the difference to initial concentration. In parallel, samples of the slices were homogenized together with their incubation fluids after the same incubation intervals. The free concentration was determined by ultrafiltration. For warfarin and several non-steroid anti-inflammatory drugs (NSAID), i.e. acetylsalicylic acid, ibuprofen, ketoprofen and oxyphenbutazone, there was no difference between the free drug concentrations in the homogenized and in non-homogenized samples. This suggests that the binding of these drugs to liver tissue was not altered by homogenization. Further was studied whether NSAIDS interfere with binding of warfarin to liver tissue. Acetylsalicylic acid, flurbiprofen, ibuprofen, ketoprofen, oxyphenbutazone and proquazon markedly increased the free concentration of warfarin both in liver slices and homogenates (p less than 0.01). The extent of displacement did not differ between slices and homogenates.

Animals↗