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Biomedical subjects

R Kroker

Publications and source records attributed to R Kroker.

At least 19 recordsLinked to original sources
PubMed1994

[Guarantee of drug quality for animal health and consumer protection].

The creation of the single market and the intended free trade of goods, individuals, capital investments and services lead to the question if the quality standards of veterinary drugs are going to be changed in view of an improved animal health and consumer protection. However, the comparison between registration and surveillance criteria that result from the German Law for Medicinal Products and the criteria valid in the European Union as a consequence of Regulations and Directives shows that no changes leading to a reduced quality are to be expected. On the contrary, the application of EU Directives to the respective national law results in a number of improvements, like for example the environmental assessment of veterinary drugs.

Animals↗
PubMed1992

[The metabolism of albendazole in the isolated perfused intestine of rats].

Pharmacokinetic studies on Albendazole after peroral administration demonstrate a rapid and complete biotransformation. The major metabolites Albendazole sulphoxide and -sulphone were detected in the plasma; the parent compound was only found sporadically at very low levels. These results indicate removal by the liver and/or the gut at first pass. After evidence is found that the liver has the capacity to sulphoxidize and to sulphonize Albendazole, biotransformation of the gut was examined using an isolated perfused rat gut model. A high-performance liquid chromatography method was used to simultaneously determinate Albendazole, -sulphoxide and -sulphone. Albendazole was biotransformed partly to Albendazole sulphoxide by the gut, whereby the metabolite but not the parent compound was absorbed. It is concluded, that the gut has the capacity to biotransform Albendazole. However, biotransformation is limited to the first step, the sulphoxidation.

Albendazole↗
PubMed1991

Investigations on the biotransformation of mebendazole using an isolated perfused rat gut system.

1. The intestinal metabolism of the benzimidazole, mebendazole (MEB), has been investigated using isolated perfused jejunal segments of rats. Significant absorption and intestinal metabolism of the substance was observed. 2. The metabolites, the reduced alpha-hydroxy-analogue, its glucuronide, and the decarbamoylated 2-amino-analogue, were transported into the resorbate collected at the serosal side or were resecreted into the gut lumen. 3. The intestinal decarbamoylation of mebendazole increased up to 20-fold after pretreatment with 3-methylcholanthrene (MC), and complete re-secretion of this metabolite into the gut lumen led to a total loss of the absorption of mebendazole and metabolites across the gut wall. 4. The results indicate the ability of the gut to metabolize mebendazole by phase I and II reactions. 5. An almost complete loss of bioavailability after induction of the gut enzyme system by MC was observed.

Animals↗
PubMed1990

The pharmacokinetics of chloramphenicol in plasma and saliva of dairy cows.

In the present study the pharmacokinetics of chloramphenicol were investigated in bovine plasma and saliva. The method of detection of chloramphenicol, a radio-immunoassay, requires only small sample volumes, no further clean-up, and a large number of samples can be processed simultaneously. This enabled the collection of a larger number of samples over a longer period of time than in previous studies. The intention was to obtain a complete pharmacokinetic profile of chloramphenicol, to evaluate it according to common open-compartment models, and to compare it with the results of previous studies. The radio-immunoassay results were confirmed by analysing a number of samples distributed over the concentration range of interest by a gas-chromatographic method with electron-capture detection. The suitability of saliva was evaluated as a possible means of monitoring compliance with the ban on chloramphenicol in the Federal Republic of Germany in milk-producing animals.

Animals↗
PubMed1985

The pharmacokinetic behaviour of chloramphenicol in liver-damaged mini-pigs.

Using mini-pigs with an indwelling vascular catheter, the pharmacokinetics of chloramphenicol were investigated in healthy and liver-damaged animals. The liver damage was induced by thioacetamide and its degree was estimated by measuring the level of bile acids in serum. Employing a two-compartment open model for analysing the time-dependent course of the chloramphenicol concentration in serum, it was shown that in liver-damaged animals the elimination half-time was almost doubled as a result of reduced total body clearance. The consequences of liver damage for withdrawal times and dosage schedules are discussed.

Animals↗
PubMed1980

Altered hepatobiliary transport of taurocholic acid in aged rats.

Hepatobiliary transport of taurocholic acid was studied in adult (3 months) and old (2 years) rats using an isolated perfused rat liver technique in order to determine the effect of age on hepatic uptake and secretion of bile acids simultaneously. The results were analyzed using a steady-state compartmental model to estimate the uptake and secretion of taurocholic acid. Hepatic secretion was decreased to a greater extent than the uptake in old rats. These changes in transport activities were associated with increases in perfusate and liver bile acid pool sizes. These results can explain the decrease in total pool size and synthesis rate of bile acids observed previously in old rats using in vivo studies. It has been suggested that the age-dependent decrease in bile acid transport capacity of the liver is secondary to the altered lipid composition of the liver plasma membranes of old rats.

Aging↗
PubMed1979

[The influence of clanobutin on bile secretion in the isolated perfused rat liver (author's transl)].

Isolated perfused rat liver was used to characterize the choleretic action of 4-[4-chloro-N-(4-methoxyphenyl)-benzamido]-butyric acid (clanobutin). The dose-dependent increase of the bile flow was associated with an increase of the Na+ secretion. In in vitro studies the drug inhibited the Na+-K+-ATPase of the sinusoidal membrane more than that of the canalicular membrane in a dose-dependent manner. The following hypothesis was proposed to explain the choleretic action of clanobutin. The intracellular Na+ concentration increased due to the inhibition of the sinusoidal Na+-K+-ATPase. This is then compensated by transporting the extra Na+ into the bile. However, it cannot be ruled out that Na+ is transported as counterion during hepatobiliary transport of clanobutin or else its metabolites. The effect of the drug seems to be non-specific since other enzymes of the plasma membrane were also inhibited.

Adenosine Triphosphatases↗
PubMed1978

A compartmental model for hepatic transport of taurocholic acid in isolated perfused rat liver.

In order to characterize the transport of bile acids through the liver and to study the influence of drugs on these processes, a kinetic model for hepatobiliary transport of taurocholic acid (TC) using the isolated perfused liver was developed. After the system was brought to a steady state by infusing TC at a constant rate, a tracer dose of 14C-TC was injected into the medium. The medium disappearance of 14C-TC followed a first-order kinetic with a single rate constant. The plot of the biliary secretion rate of radioactivity versus time revealed a curve composed of at least three exponential components. From the described results and the present knowledge of hepatobiliary transport of bile acids we proposed a three compartment model, composed of a perfusion medium compartment and two liver compartments. Parameters calculated from the model constants agreed well with model-independent estimations. The influence of bromosulfophthalein (BSP) on the kinetic parameters was studied to compare the result with the known effect of BSP on hepatic transport of taurocholic acid. BSP decreased the constant describing the fractional transfer of taurocholic acid from medium into the liver, which is in agreement with the inhibition of hepatic uptake of taurocholic acid by BSP. Thus a three compartment model may adequately define the hepatobiliary transport of taurocholic acid in the isolated perfused rat liver.

Animals↗
PubMed1978

The lack of active bile acid transport in AS-30 D ascites hepatoma cells.

The uptake of cholic acid as well as taurocholic acid into AS-30 D ascites hepatoma cells showed linearity with respect to incubation concentrations. It has been suggested that these processes can be described as simple diffusion. In further experiments it could be shown that ascites hepatoma cells were unable to conjugate cholic acid. These results may have significance in the phalloidin action on hepatocytes.

Animals↗
PubMed1978

The interaction of rifamycin SV with hepatic transport of taurocholic acid in the isolated perfused rat liver.

The effect of rifamycin SV on hepatic transport of taurocholic acid was investigated using isolated perfused rat liver technique. In all experiments, the perfused liver was maintained at taurocholic acid steady state by infusing constant amount of taurocholic acid. Infusion of rifamycin SV at various rates decreased biliary secretion of bile acids in a dose-dependent manner. Replacement of rifamycin SV by perfusion medium reversed this effect. To determine the site of action of rifamycin SV, kinetic experiments with 14C-taurocholic acid were undertaken. Rifamycin SV elevated the half-life of the medium disappearance of 14C-taurocholic acid. Furthermore, the antibiotic delayed the biliary appearance of 14C-taurocholic acid. The analysis of the results gave indications that the antibiotic interferred with hepatic uptake as well as biliary secretion of taurocholic acid.

Animals↗
PubMed1978

Inhibition of hepatic uptake of bile acids by rifamycins.

The effect of rifamycin SV and rifampicin on hepatic acid uptake was studied using isolated rat hepatocytes in presence and in absence of albumin. The drugs inhibited cholate uptake more than taurocholate uptake and the inhibition was of non-competitive type. In presence of 3% albumin the inhibitory effect of the drugs was more for cholate and less for taurocholate uptake than in absence of albumin. Neither the binding of bile acids nor that of the drugs to albumin was altered by one another. Thus the effect in presence of albumin cannot be explained by the binding of the drugs and bile acids to albumin alone. It is suggested that albumin interacts with hepatic bile acid uptake process and this interaction with cholate uptake is different from that with taurocholate uptake. This additional and different effect of albumin may explain the effect of the drugs in presence of albumin. The results may be of clinical significance in rifamycins treatments.

Albumins↗
PubMed1977

Cholic acid binding to isolated rat liver plasma membranes.

Cholic acid binding to isolated rat liver plasma membranes was studied using a centrifugal filtration technique which allowed independent determination of free and membrane-bound cholic acid. Binding of cholic acid was very rapid and reversible. Scatchard analysis revealed at least three binding sites with high, medium and low affinity. The high affinity binding a) displayed saturability and isotope replacement, b) was not present in rat liver mitochondria and red blood cell ghosts and c) was temperature dependent. This binding has a very low capacity with a dissociation constant in the physiological range of plasma cholic acid concentration and has an affinity for other common bile acids. Cholic acid binding to the high affinity binding site was not inhibited by estrone, beta-estradiol or cholesterol. These results would suggest that the high affinity binding site represents a specific binding site for cholic acid and may also be specific for other common bile acids. This binding was not dependent on Na and was inhibited by bromosulfophthalein. Cholic acid binding to the high affinity site has some features in common with cholic acid uptake by isolated rat hepatocytes, and this would suggest that the high affinity binding site could be the postulated carrier for hepatic uptake of cholic acid.

Animals↗
PubMed1977

The age dependence of bile acid metabolism in rats.

The age dependence of bile acid metabolism in rats was investigated and the following results were obtained. 1) Synthesis rate, pool size and total secretion decreased in old rats (24 month) significantly compared to young rats (6 weeks). 2) The quotient of taurine to glycine conjugates is is significant lower in old rats compared to young rats. 3) The lithogenic index remains unchanged in all age groups. 4) Old rats show a significantly higher Km for cholic acid uptake, whereas the diffusion coefficient is decreased. The possible influence of humoral factors on age dependent regulations of bile metabolism is discussed.

Age Factors↗
PubMed1977

Characterization of methylumbilliferone (mendiaxon r)-induced choleresis in the isolated perfused rat liver.

The influence of the choleretic drug methylumbilliferone on bile formation in the isolated perfused rat liver is characterized. The compound induces rapidly an elevation of bile flow, bile acid secretion and soium excretion. The increased production of bile is of canalicular origin. The choleretic effect was defined as "bile acid like" choleresis due to excretion of the drug into the bile. It is discussed that the excretion of methylumbilliferone can influence the transport of bile in form of a positive cooperation on transport mechanism.

Animals↗