bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mean residence time of drugs administered non‐instantaneously and undergoing linear tissue distribution and reversible metabolism and linear or non‐linear elimination from the central compartment
Authors: Cheng Haiyung 
Published: October 2006

AbstractBased on disposition decomposition analysis (DDA), equations for the mean residence times (MRT) in the body are derived for a drug and its interconversion metabolite that undergo linear tissue distribution and linear or non‐linear elimination from the central compartment after non‐instantaneous administration of the drug. The MRT of the drug after non‐instantaneous input can be related to the MRT of the drug after intravenous administration, the ratio of the total area under the plasma concentration—time curve of the drug after non‐instantaneous administration to that after intravenous administration, the bioavailability of the drug, and the mean input time of the drug. Similar relationships also exist for the MRT of the interconversion metabolite after non‐instantaneous input of the drug. The application of these equations to a non‐linear reversible metabolic system is illustrated with computer simulations.
Pharmacokinetics and hepatic first‐pass effect of (−)‐carbovir in the anesthetized rat
Authors: Soria Inmaculada , Zimmerman Cheryl L. 
Published: October 2006

AbstractStudies were designed to allow an in vivo estimation of the hepatic extraction ratio and to test the hypothesis that the pharmacokinetic parameters of (−)‐CBV are significantly different during anesthesia. (−)‐CBV was administered as an IV bolus followed by IV infusion into either the portal (n = 3) or the jugular (n = 3) veins of anesthetized male Sprague—Dawley rats These studies indicated that (−)‐CBV had a very low hepatic extraction ratio, in agreement with previous (−)‐CBV in situ liver perfusion studies. Additionally, anesthesia was shown to alter the pharmacokinetics of (−)‐CBV by reducing the total body clearance of this drug.
Pharmacokinetics of α‐dihydroergocriptine in rats after single intravenous and single and repeated oral administrations
Authors: Coppi G. , Silingardi S. 
Published: October 2006

AbstractThe pharmacokinetics of α‐dihydroergocriptine methane sulphonate in rats were investigated using an HPLC method for the detection of unchanged α‐dihydroergocriptine (DHEK) in plasma, organs (kidneys, heart, lungs, spleen, liver, and brain), and urine. The plasma profile of DHEK obtained after intravenous administration at a dose of 5 mg kg−1 (as base) of DHEK methane sulphonate showed a three compartment pharmacokinetic model with an elimination half‐life of 6.78 h. The kinetics of DHEK after a single oral administration at a dose of 20 mg kg−1 (as base) showed two peaks: the second peak, at about 6 h, was probably due to an enterohepatic cycle. The disposition of DHEK consisted of an absorption half‐life of 0.02 h, a distribution half‐life of 2.15 h and an elimination half‐life of 5.83 h. The pharmacokinetics of DHEK, after repeated oral administrations at the same dose, were similar to those after a single oral administration. The absolute bioavailability was 4.14% after a single oral administration and 3.95% after repeated oral administrations. The analysis of the organs showed that DHEK was rapidly absorbed and distributed in all tissues, mostly in lungs, kidneys, and liver, but it is interesting to observe that it also reached the brain. After repeated oral administrations plasma and tissue concentrations were similar to those obtained after a single administration; therefore it is possible to exclude the onset of autoinduction or accumulation phenomena of DHEK in rats' organs.Urinary excretion of the unchanged drug was low (0.38% of the administered dose in the intravenous route and 0.04% in the oral route), being in agreement with a low oral bioavailability and a rapid and extensive metabolism (first‐pass effect).
Pharmacokinetics of reboxetine in healthy volunteers. Single oral doses, linearity and plasma protein binding
Authors: Edwards D. M. F. , Pellizzoni C. , Breuel H. P. , Berardi A. , Castelli M. G. , Frigerio E. , Poggesi I. , Rocchetti M. , Dubini A. , Benedetti M. Strolin 
Published: October 2006

AbstractThe pharmacokinetics of reboxetine, a new antidepressant agent, were found to be close to linear in a crossover study comparing administration of single 2, 3, 4 and 5 mg capsule doses in 15 healthy male volunteers, and in the same study the capsules were bioequivalent to the proposed therapeutic tablet formulation (4mg). Kinetic analysis was based on HPLC assay of reboxetine in plasma and urine collected up to 72 h after each administration. Plasma levels indicated a rapid absorption (tmax⋍2h) and an elimination half‐life of about 13 h. Clearance and volume of distribution were modest (ratios to bioavailability: CL/F⋍29 mL min−1; Vz/F⋍32L); urinary excretion was ∼9% of dose, corresponding to a renal clearance of only 3 mL min−1 (a value consistent with the rate of glomerular filtration of unbound drug). In vitro, binding to plasma proteins, estimated from radioactivity levels following dialysis of 14C‐labelled reboxetine, appeared to be dominated by α1‐acid glycoprotein without marked saturation up to plasma concentrations of over 500 ng mL−1 (2.8–3.1% unbound with human plasma from three additional volunteers; 1.8–2.0% for 2gL−1 orosomucoid α1‐acid glycoprotein, and 46.4–47.4% for 40 gL−1 albumin), whilst the mean Cmax in the current study was much lower (164 ng mL−1 after a 5 mg dose).
Selective adherence of a sucralfate—tetracycline complex to gastric ulcers: Implications for the treatment of Helicobacter pylori
Authors: Yokel Robert A , Dickey Kenneth M. , Goldberg Arthur H. 
Published: October 2006

AbstractThe adherence of a sucralfate—tetracycline complex to gastric ulcers and to nearby nonulcer sites was determined in the rabbit antrum. Persistent gastric ulcers were produced by a previously described method. The presence of the complex was assessed 1 and 4 h after dosing. Drug adherence was determined by quantitation of aluminum in stomach wall biopsies. Significantly more aluminum adhered to ulcer sites than to nearby nonulcer sites. Adherence of the complex did not significantly decrease from 1 to 4 h. The complexation of tetracycline to sucralfate did not alter the selective adherence of sucralfte to gastric ulcers, providing a mechanism of ulcer site‐selective drug delivery in the treatment of Helicobacter pylori gastric ulcer disease.
Pharmacokinetics and relative bioavailability of selegiline in healthy volunteers
Authors: Mahmood Iftekhar , Marinac Jacqueline S. , Willsie Sandra , Mason William D. 
Published: October 2006

AbstractSelegiline is beneficial to Parkinsonian patients as an adjunct to levodopa therapy. A sensitive fluorimetric assay based on ibhibition of rat brain monoamine oxidase‐B (MAO‐B) in vitro has been developed to study the pharmacokinetics of selegiline. This method quantitates selegiline as low as 0.25 ng ml−1. The pharmacokinetics and relative bioavailability of selegiline were investigated in healthy volunteers following oral administration of 10 mg tablet or solution. A half‐life of approximately 70 min was observed following the administration of either dosage form. Although the two dosage forms exhibited a lag time, the absorption was rapid and peak plasma concentrations were observed between 30 and 45 min for the solution and 30 and 90 min for the tablets. Statistically no significant difference was found between Cmax, Tmax, AUC0‐∞ and MRT between the two dosage forms. Negligible renal clearance was found in both groups, but aparent oral plasma clearance was comparatively high and indicates rapid elimination of selegiline from the body.
Stability, tissue metabolism, tissue distribution and blood partition of azosemide
Authors: Lee Sun H. , Lee Myung G. 
Published: October 2006

AbstractStability of azosemide after incubation in various pH solutions, human plasma, human gastric juice, and rat liver homogenates, metabolism of azosemide after incubation in 9000g supernatant fraction of various rat tissue homogenates in the presence of NADPH, tissue distribution of azosemide and M1 after intravenous (IV) administration of azosemide, 20 mg kg−1, to rats, and blood partition of azosemide between plasma and blood cells from rabbit blood were studied. Azosemide seemed to be stable for up to 48 h incubation in various pH solutions ranging from two to 13 at an azosemide concentration of 10 μg mL−1; more than 93.4% of azosemide was recovered and a metabolite of azosemide, M1, was not detected. However, the drug was unstable in pH 1 solution: 75.8% of azosemide was recovered and 2.16 μg mL−1 of M1 (expressed in terms of azosemide) was formed after 48 h incubation in pH 1 solution at an azosemide concentration of 10 μg mL−1. Azosemide was stable in both human plasma and rat liver homogenates for up to 24 h incubation at an azosemide concentration of 1 μg mL−1, and in human gastric juice for up to 4 h incubation at an azosemide concentration of 10 μg mL−1. However,‐all rat tissues stdied had metabolic activity for azosemide in the presence of NADPH, with heart having a considerable metabolic acitivity: approximately 22% of azosemide disappeared and 9.32 μg of M1 was formed per gram of heart (expressed in terms of azosemide) after 30 min incubation of 50 μg of azosemide in 9000g supernatant fraction of heart homogenates. The tissue to plasma ratios of azosemide (T/P) were greater than unity only in the liver (1.26) and kidney (1.74); however, M1 showed high affinity for all tissues studied except the brain and spleen when each tissue was collected at 30 min after IV administration of azosemide to rats. The equilibrium plasma to blood cell concentration ratios of azosemide were independent of azosemide blood concentrations: the values were 2.78–4.25 at azosemide blood concentrations of 1, 10, and 20 μg mL−1 three rabbits. There was negligible ‘blood storage effect’ of azosemide, especially at low blood concentrations of azosemide, such as 1 and 10 μg mL−1.
Stability and pharmacokinetic studies of a new immunosuppressant, mycophenolate mofetil (RS‐61443), in rats
Authors: Sugioka Nobuyuki , Chen Shi Hu , Hayashida Kazuhisa , Koyama Hikaru , Ohta Toshio , Kishimoto Hideki , Yasumura Tadaki , Takada Kanji 
Published: October 2006

AbstractMycophenolate mofetil (MPM), a new immunosuppressant, is a morpholinoethyl ester of mycophenolic acid (MPA). The enzymatic and non‐enzymatic hydrolysis was studied in an artifical digestive fluid, rat plasma, and tissue homogenates. MPM was chemically stable in the artificial digestive fluid. In rat tissue homogenates and plasma, MPM was rapidly hydrolysed to MPA. The conversion rate of MPM to MPA in various rat tissue homogenates was in the order of liver > kidney > plasma > small‐intestinal epithelial cells. After the intravenous injection of MPM at 16.7 mg kg−1, the terminal elimination half‐life,‐t1/2β, was 4.74 ± 0.33 (mean ± SD)h, and the area under the plasma concentration versus time curve, AUC, was 48.78 ± 6.01 μg h mL−1. After intraduodenal (ID) administration of MPM at 16.7 mg kg−1, t1/2β was 3.92 ± 1.05 h, and the AUC was 38.08 ± 8.30 μg h mL−1. The systemic availability of MPA after ID MPM dosing was 1.52 times higher than that after ID administration of MPA. This result supports the usefulness of MPM as an oral produrg of MPA as a new oral immunosuppressant.
Comparison of plasma and saliva concentrations of the active monohydroxy metabolite of oxcarbazepine in patients at steady state
Authors: Cardot J.‐M. , Degen P. , Flesch G. , Menge P. , Dieterle W. 
Published: October 2006

AbstractA study was performed in ten patients, stabilized with oxcarbazepine monotherapy (450–750 mg bid) for two weeks minimum, to investigate the possibility of using saliva to monitor the oxcarbazepine therapy. Thirteen paired blood and saliva samples were taken over 24h. The saliva samples were obtained after stimulation.The analysis performed on the data suggests a dose dependence for the relationship between plasma and saliva concentrations of the main active metabolite, 10, 11‐dihydro‐10‐hydroxycarbamazepine (MHD), and the importance of the type of stimulation for the saliva's production. Therefore it would be preferable to use plasma concentrations to monitor oxcarbazepine therapy, if necessary.
Pharmaceutical and biological properties of doxorubicin encapsulated in liposomes (L‐ADM): The effect of repeated administration on the systemic phagocytic activity and pharmacokinetics
Authors: Yachi Kiyoto , Kikuchi Hiroshi , Suzuki Norio , Atsumi Ryo , Aonuma Masashi , Kawato Yasuyoshi 
Published: October 2006

AbstractWe investigated the biodistribution and antitumour activity of doxorubicin (ADM) encapsulated in liposomes (L‐ADM) after two administrations in tumour bearing mice. The effect of the first administration on phagocytic activity was also examined.The biodistribution of L‐ADM after the second dosing at an interval of 4d was remarkably different from that after the first. The concentration of ADM in plasma and tumour after the second injection was higher, but that in the liver was lower than after the first administration. This decrease in distribution to the liver is thought to have contributed to the difference in the biodistribution characteristics of L‐ADM. With regard to antitumour effect, the activity was similar between L‐ADM and a solution of ADM (F‐ADM).To investigate the effect of the first administration of L‐ADM on biodistribution, systemic phagocytic activity was measured after the injection of F‐ADM, L‐ADM, or ‘empty’ liposomes not containing ADM. F‐ADM and L‐ADM (7.5 mg ADM/kg body weight) reduced phagocytic activity to approximately 50% and 30% of control, respectively. This finding suggests that entrapment of ADM in liposomes enhances both the distribution of the drug to the reticuloendothelial system (RES) and its suppressive effect on RES activity.These results indicate that the decrease in RES activity by L‐ADM must be considered in estimation of the pharmacokinetics, antitumour activity, and toxicity of L‐ADM in clinical use when given by repeat administration or used in combination with other antitumour agents.
Pharmacokinetics of terbinafine and of its five main metabolites in plasma and urine, following a single oral dose in healthy subjects
Authors: Humbert H. , Cabiac M. D. , Denouël J. , Kirkesseli S. 
Published: October 2006

AbstractThe plasma pharmacokinetics, and the urinary excretion, of terbinafine and its five main metabolites have been investigated after a single oral dose administration of 125 mg to 16 healthy subjects.In plasma, the highest concentrations are observed for the two carboxybutyl metabolites, with a predominance for the carboxybutylterbinafine. For this metabolite, as compared to terbinafine, the Cmax and AUC are 2.4 and 13 times higher respectively. The demethylterbinafine presents a plasma profile close to that of terbinafine. The two hydroxy metabolites are only found as glucuronide and are of minor importance. The apparent terminal half‐lives of terbinafine, demethylterbinafine, and the two carboxy metabolites appear to be similar (∼ 25h). As compared to the plasma concentration of total radioactivity observed after a single oral administration of the same dose of 14C‐terbinafine, the parent drug and these five metabolites, account for more than 80% of the total radioactivity in plasma over the 0–48 h interval following administration.In urine, the major metabolite is demethylcarboxybutylterbinafine, which amounted to about 10% of the administered dose. Terbinafine and demethylterbinafine are only excreted as trace amounts in urine. Carboxybutylterbinafine and the two hydroxy metabolites are excreted in the range of 0.5–2% either as glucuronides or free. Urinary excretion over the 0–48h interval of terbinafine and of the five metabolites amounted to about 14% of the administered dose. This is far below the level of total radioactivity measured in urine over the same interval (∼ 57%), after administration of 14C‐terbinafine. This shows in contrast to plasma, that numerous other metabolites are present in urine.
Interspecies pharmacokinetic scaling of BSH in mice, rats, rabbits, and humans
Authors: Mehta Samir C. , Lu D. Robert 
Published: October 2006

AbstractSodium mercaptoundecahydrododecaborate or BSH is an important compound for boron neutron capture therapy (BNCT). The total clearance and steady state volume of distribution of BSH in humans and in laboratory animals were analyzed as a function of species body weight using the allometric equation for interspecies scaling. Significant linear relationships were obtained between log CLt (L h−1) and log W(kg) (r=0.972; p=0.028) as well as log VSS(L) and log W(kg) (r=0.999; p=0.0005). The corresponding allometric equations were CLt=0.127 W0.68 and VSS=1.557 W0.87, respectively. BSH clearance in various species was shown to be a constant fraction (0.26) of creatinine clearance, the relationship being independent of body weight. Thus BSH clearance in various species occurred at similar pace when measured by a physiological parameter (creatinine clearance) rather than chronological time. Interspecies scale‐up of plasma concentration—time data for the four species using a complex Dedrick plot resulted in similar profiles. Our results indicate that the BSH data obtained in laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters in humans. These parameters can serve as guidelines for better planning of clinical studies.
Antibronchospasmic, tachycardiac, and hypokalaemic effects of L‐isoproterenol in guinea‐pigs
Authors: Ohtani Hisakazu , Yamamoto Koujirou , Sawada Yasufumi , Iga Tatsuji 
Published: October 2006

AbstractThe relationship between antibronchospasmic, tachycardiac, or hypokalaemic effects and plasma concentration of L‐isoproterenol (ISP) hydrochloride was investigated in guinea‐pigs in vivo. ISP was infused at the rate of 10, 30, 50, 100, and 300 ng kg−1 min−1. The antibronchospasmic effect was expressed as the attenuation of methacholine‐induced bronchospasm. The EC50 values of ISP for antibronchospasmic and tachycardiac effects were 5.12 nM and 3.95 nM, respectively. Although they were comparable to the values reported in vitro (7.23–0.358 nM, 1.77 nM), the concentration response relationship of ISP for antibronchospasmic effect was quite steep with a slope factor of more than six. Moreover, a decrease in plasma potassium level was not clearly detected. The experimental procedure in our present study was useful for evaluating antibronchospasmic and tachycardiac effects of beta‐agonists.
Niedergang der Vergleichenden Morphologie ‐ Verlust für die Botanik
Authors: Mollenhauer Dieter 
Published: October 2006

AbstractComparative or idealistic morphology can be taken for one of many different kinds of approaches in general biology. Its Golden Age was the era of Central European Romanticism, one late descendant of this tradition was Wilhelm Troll (1897‐1978). In the end of the 19th century morphology stood back. Its place in the front scene was taken by other general approaches. At present, however, aphilosophic or even antiphilosophic specialists with their materialistic ideologies (of which they are mainly unconscious) are setting the fashion in biology. General concepts are suspicious of natural philosophy and not wanted. If forwarded they have little influence on actual research. Desultory activity is characteristic of present‐day biology resulting in masses of incoherent data. However, history shows how much general concepts are needed for alignment of scientific research. One reason for the vanishing interest in general concepts can be found in professionalized science. Professionalism included the trend to confine to internal affairs. This ends up with a confrontation of two parties: scientists who dispose of knowledge and the public without such insight. Scientists, however, beware of surpassing their “proper spheres of responsibility” thus leaving the public in full obligation to decide on plans, enterprises, and operations. Positive science therefore turns out to be science in complete disengagement since it is pure expert knowledge. Biology must escape from positivism. It needs vital general concepts, otherwise it remains esoteric, exclusive and isolated. Science without interference with actual culture is as sterile and only for luxury as is art in its l'art‐pour‐l'art attitude.
Auflösung durch Unterwanderung
Authors: Schröder Susanne 
Published: October 2006

AbstractLes raisons pour lesquelles la littérature comparée en Allemagne n'a pas réussi à s'établir en tant que discipline académique pendant l'époque de Wilhelm II et de la République de Weimar (1871‐1933) peuvent s'expliquer sous deux aspects différents.‐ Si l'on tient compte de l'histoire des idées la ‘Geistesgeschichte’ vint remplacer le positivisme. Cette ‘Geistesgeschichte’ qui d'un cǒté refusait le mécanisme des études des influences et de la ‘Stoffgeschichte’, affirmait de son cǒté son engagement pour les intérêts du comparatisme (l'étude des grands courants européens).‐ Du point de vue politique, c'est la germanistique avec ses buts nationalistes qui empecha le comparatisme, centré sur l'entente des peuples et les vrais échanges internationaux, de s'installer à l'Université.
Lavoisier, Lichtenberg und Heisenberg
Authors: Wagner Siegfried 
Published: October 2006

AbstractThe essay deals with the remarks on scientific revolutions, as well as on paradigms by some revolutionaries in science. ‐In 1772 Lavoisier remarked in his laboratory note‐book that he was going to make a revolution in chemistry and in physics by replacing the concept of phlogiston by oxygen. During the French revolution, Condorcet came to the conclusion that there are times of stagnation in science, whereafter a genius invents new methods. Both authors were among the three members of the Académie des Sciences who became victims of the Revolution. Lichtenberg was only a spectator of the Revolution. But the [revolutions on Earth] (as he called the Earth quakes) inspired him to contemplate scientific revolution. In the sketch of a textbook on science which he composed during the 1790's, and which he never completed, Lichtenberg returned to this topic. Here he introduced the concept of the paradigm as a tool in science. This term was defined according to its original meaning in classical Greek, i.e. as a model which is taken from a well established branch of science and is applied to a science as yet to be developed. In addition, Lichtenberg discussed several cases in which two scientific hypotheses were in contest. He believed that the future theory would contain a synthesis of the two opposing concepts rather than mark the victory of one over the other.Heisenberg expressed, since 1932, his views on the development of science in several lectures adressed to the general public. His conclusion was that in sciences, from time to time, revolutions occur in which a given theory will be transformed in the sense of a metamorphosis; the new theory will then be based on a different system of basic concepts. The reasons for a revolutionary transformation are experimental data which do not fit the old theory. During this process the well established older theory is neither falsified nor completely replaced by the new one which, however, ordains the limits of its validity. Heisenberg signifies such theories (as the classical, the relativistic, or the quantum mechanics) as closed theories which are always true. He generalized his own experience in this way: A scientific revolutionary never starts with abandoning the older theory, on the contrary, he wants to save as much of it as possible‐and thus unwittingly he achieves a revolution.