[In vitro studies of drug transport--methods, results, mechanisms].
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Biological Transport, Active↗
Biomedical subjects
R Neubert
Publications and source records attributed to R Neubert.
Ion pair transport across membranes.
The present review discusses drugs and counter ions suitable for ion pair transport (IPT). Ion pairing is shown to effectively increase the lipophilicity and transport rate of polar drugs across lipid membranes. The proposed mechanisms of IPT are discussed in detail. A marked change in drug properties upon ion pair formation is necessary to improve the bioavailability of hydrophilic ionizable drugs.
Animals↗
Influence of the ion-pair-formation on the pharmacokinetic properties of drugs. Part 5: Influence of ion-pair-formation on elimination of bretylium and hexylsalicylic acid in rats.
Following i.v. administration of the hydrophilic drug bretylium (1) and the lipophilic hexylsalicylic acid (2) in rats the plasma levels of 2 were increased due to an increased intestinal reabsorption of 2. Under these conditions the biliary eliminated amount of 2 was 8 times higher than that following the administration of 2 alone. The eneteroheptic circulation of 2 was found to be interrupted following i.v. administration of 1 and 2 and additional oral administration of an anionic exchanger. Then the plasma levels of 2 were not influenced by 1. On other hand the plasma levels of 2 appear to be too low in order to influence those of 1.
Animals↗
Immuno-toxicology and -pharmacology.
1. The new field of immunotoxicology may be expected to gain considerable importance in the assessment of possible toxic risks of chemicals. It is an applied science based on the considerable experience gained in basic immunological research within the last decades. 2. Some possibilities are discussed and procedures suggested for evaluating toxic effects induced by chemicals (including drugs) in experimental animals and man. 3. Original data are presented on thymus atrophy induced in the offspring of rats treated on day 10 of pregnancy with the virostatic drug acyclovir. 4. Experimental data are presented on the effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the distribution of lymphocyte populations (peripheral blood) in primates in vivo and in vitro, as determined with monoclonal antibodies as probes.
Acyclovir↗
[Ampicillin ion pair transport in comparison with the transport of other penicillins].
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Ampicillin↗
[Synthesis, detection and pharmacokinetic behavior of pholedrine sulphate esters. 7. Comparison of free- and sustained-release tablets in vivo and in vitro].
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Amidines↗
[Bronchoalveolar lavage in patients with sarcoidosis--methodologic aspects of the collection, immunologic characterization of lymphocytes and studies of immunoglobulin content].
The activity of alveolitis in 25 patients with pulmonary sarcoidosis was determined by analysis of T-Lymphocytes and their subpopulations collected by broncho-alveolar lavage. The characterization of the lymphocytes was performed with monoclonal antibodies (BL-series). An amount of T-lymphocytes higher than 28% of all cells and a proportion of T4/T8-lymphocytes of 8:1 and over are signs of the activity of the alveolitis and an indication for corticoid therapy.
Antibodies, Monoclonal↗
[Drug transport through artificial lipoid membranes. 22. Amplitude of ultrasonicated liposomes as a model system for investigations of drug transport].
The use of sonicated liposomes for the characterization of the transport behaviour of basic drugs is described. The rate of permeation depends mostly on the lipophilic character of the drugs.
Chemical Phenomena↗
Influence of ion-pair-formation on the pharmacokinetic properties of drugs. Part 3: Influence of hexylsalicylic acid on the pharmacokinetics of pholedrine.
Based on previous in vitro studies it could be shown that ion-pair-formation with the lipophilic hexylsalicylic acid (1) influences the pharmacokinetics of the hydrophilic drug pholedrine (2) which is ionized in all physiological media. After oral combination with 1 an increase of the AUC of 2 could be observed. This finding is due both to the increase of the absorption of 2 and to the decrease of the elimination of 2. After i.v. application the high biotransformation rate of 2 prevents an influence of 1.
Administration, Oral↗
Influence of ion-pair-formation on the pharmacokinetic properties of drugs. Part 4: Influence of hexylsalicylic acid on the pharmacokinetics of bretylium.
Based on in vitro results it was found that the pharmacokinetic parameters of the hydrophilic drug bretylium (2) can be influenced by an ion-pair-formation with the lipophilic hexylsalicyclic acid (1). After simultaneous i.v. application of 1 and 2 on rabbits a significant increase of the AUC of 2 was observed. Under these conditions a marked increase of the AUC and the MRT of 1 was also obtained, since the blood levels of 2 are high enough for such an influence. A combined rectal application of 1 and 2 causes an increase of the AUC of 2.
Administration, Oral↗
[Production, analysis and pharmacokinetic behavior of pholedrin sulfuric acid esters. 1. Production and analysis of pholedrin sulfuric acid esters].
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Chemical Phenomena↗
[The effect of ion pair formation on the pharmacokinetic properties of drugs. 1. The effect of alpha-methylpalmitic acid on the pharmacokinetics of quinine in rabbits].
The transport of quinine through artificial lipid membranes is significantly increased by use of alpha-methylpalmitinic acid (alpha-MPS). Using rabbits it could be shown that the alpha-MPS causes a significant increase of the mean resistance time (MRT) of quinine. Besides the alpha-MPS causes an increases Cmax and a shorter tmax of the quinine blood levels.
Animals↗
[Drug permeation through artificial lipoid membranes. 20. The effectiveness of multiple-lamellar liposomes for evaluating drug transport].
The use of stable liposomes for distribution experiments with some drugs is described. Great differences between distribution coefficients liposomes/water and n-octanol/water were found.
Liposomes↗
[Drug transport through artificial lipoid membranes. 21. Ion pair transport with alkyl salicylic acids].
Using hexylsalicylic acid it was demonstrated that alkylated derivatives of salicylic acid are able to increase partition and transport of ionized basic drugs across lipophilic membranes. The influence of different donor concentrations on the relation of transport was studied by means of pholedrine in combination with hexylsalicylic acid. In order to explain the mechanism of the ion-pair-transport experiments were carried out which show beside the mentioned increase of transport the occurrence of a countertransport of protons and lithium-ions, respectively. The lipophilic counterion hexylsalicylate acts inside of this mechanism as a carrier for the ionized drugs.
Chemical Phenomena↗
[The effect of ion pair formation on the pharmacokinetics of drugs. 2. The effect of hexylsalicylic acid on the pharmacokinetics of quinine].
The influence of the hexylsalicylic acid (2) on the pharmacokinetic of the quinine (1), was studied using rabbits. It could be observed that after i.v. application the mean resistance time (MRT) of 1 was increased by means of ion-pair-formation with 2. But the AUC of 1 was not influenced. After rectal application of the combination 1/2 an acceleration of the 1 absorption could be pointed out. The kinetic parameters of 2 were not increased significantly if 1 was applicated simultaneously.
Administration, Rectal↗
[A new experimental design for the in vitro evaluation of drug absorption in topical forms. 1. Design and model calculation].
An in-vitro model is presented which consists on several membrane Layers. The penetration of drugs from the ointment bases into these membrane Layers is observed. By combination of different membranes this system can be varied. In model calculations the resulting conditions are demonstrated.
Administration, Topical↗
[Possibilities for the in vitro evaluation of bioavailability. 5. Compact peroral agents with basic drugs].
Lipophilic, basic drugs can be transported across lipoid-membrane even if the part of the substance being not ionized in the solution is very low. Therefore the resorption model can be used for the control of drugs containing the substances as salts. In the case of 4 substances no differences could be found concerning half transport time between the aqueous solutions and the drugs.
Administration, Oral↗
[Action of [3,14-L-selenocysteine, 8-D-tryptophan]-somatostatin on insulin and glucagon secretion of the isolated perfused pancrease of the Wistar rat].
By isolated perfused pancreas of Wistar rats the glucose (11 mmol/l) and arginine (10 mmol/l) stimulated insulin (IRI) and glucagon (IRG) secretion was measured in order to investigate the inhibitory activities of somatostatin-14 (SS 14) and the somatostatin analogue [3,14-L-seleno-cysteine, 8-D-tryptophan]-somatostatin (SeSS). SS-14 or SeSS (152.8 nmol/l) inhibit the glucose stimulated IRI secretion by 75 and 65%, respectively. Only the second phase of the biphasic arginine stimulated insulin secretion pattern by 40%. SeSS has under these conditions no effect, whereas 58 nmol/l SS-14 or SeSS show a suppressing effect on the first (20 and 55%, respectively) and second phase (65 and 85%, respectively) of the insulin secretion. Using 5.8 nmol/l SS-14 or SeSS the arginine stimulated IRG secretion was inhibited only in the second phase of the biphasic glucagon secretion pattern by about 40%. 58 nmol/l SS-14 or SeSS show an inhibiting effect on the first and on the second phase of secretion, in both cases about 50%. It is concluded that in the SS-14 molecule the sulfur of cysteine in position 3 and 14 can be exchanged by selenium without modifying the biological activities measured in the glucose or arginine stimulated IRI and IRG secretion in vitro. The D-Trp8 in the SeSS analogue does not show the typical better inhibitory action of D-Trp8-SS-14 on insulin and glucagon secretion compared with SS-14. Possibly the selenium in the SeSS analogue abolishes this effect.
Animals↗