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  • 1
    Electronic Resource
    Electronic Resource
    Pharmakokinetik und Dosierung von Dextran 40 in Abhängigkeit von der Nierenfunktion (1974)
    Springer
    Journal of molecular medicine 52 (1974), S. 1111-1116 
    Details
    ISSN: 1432-1440
    Keywords: Dextran 40 ; elimination ; renal function ; Dextran 40 ; Elimination ; Nierenfunktion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 36 Patienten mit unterschiedlicher Nierenfunktion (GFR zwischen 0,5–142 ml/min) erhielten 500 ml 10%iges Dextran 40 (Rheomacrodex®). Dabei ergab sich ein relatives Verteilungsvolumen von 10,2±2,2 1/100 kg. Die Eliminationshalbwertzeiten von Dextran 40 stehen mit der Nierenfunktion (51 Cr-EDTA-Clearance) in einem Zusammenhang, der sich rechnerisch am besten durch eine Potenzfunktion darstellen läßt. Patienten mit normaler Nierenfunktion (GFR über 90 ml/min) haben eine Eliminationshalbwertzeit von 573±138 min und eine 12 Std-Recovery im Urin von 48%. Ein Glomerulusfiltrat unter 10 ml/min führt dagegen zur Verlängerung der Halbwertzeit auf das Fünffache (Dextran 40-HWZ=2591±1022 min) und zum Rückgang der 12 Std-Recovery auf 4%. Im Clearancebereich zwischen 30 und 142 ml/min bleiben Eliminationshalbwertzeit und Urinausscheidung im wesentlichen konstant. Dextran 40 kann deshalb bei diesen Patienten nach den bekannten Regeln dosiert werden. Bei glomerulären Filtrationswerten unter 30 ml/min ist jedoch mit einer gestörten Elimination zu rechnen. Aus der veränderten Dextran 40-Ausscheidung im Urin und aus den Eliminationshalbwertzeiten ergeben sich Dosierungsrichtlinien, die diskutiert und tabellarisch aufgeführt werden.
    Notes: Summary 36 patients with different renal function (GFR=0.5−142 ml/min) received 500 ml of 10% dextran 40 (Rheomacrodex®). The relative distribution volume proved to be 10.2±2.21/100 kg. Dextran 40 half life time and renal function are correlated mathematically as a power function. In patients with normal renal function (GFR〉90 ml/min) we determined a dextran 40 half life time of 573±138 min and a 12 hour urinary recovery of 48%. In contrast to that a glomerular filtration rate below 10 ml/min prolongs the half-life five times to a value of 2591±1022 min and reduces the urinary elimination to 4% per 12 hours. In patients with a clearance between 30 and 142 ml/min no essential changes of half life time and urinary elimination can be observed. To those patients dextran 40 can be applied in the common dosage. Contrary to that a glomerular filtration rate below 30 ml/min leads to a prolonged elimination and consequently a different dosage has to be applied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468621
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  • 2
    Electronic Resource
    Electronic Resource
    Die immunologische und funktionelle Protein C-Bestimmung bei verschiedenen internistischen Erkrankungen (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 906-911 
    Details
    ISSN: 1432-1440
    Keywords: Protein C activity ; Protein C antigen ; Malignancy ; DIC ; Liver disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A new practicable and precise functional protein C evaluation test is based on the activation of protein C by a snake venom activator and determination of PC activity by its property to prolong the aPTT in a clotting assay (VK=1.9% and 4% for intra- and interassay variance respectively). In 40 healthy controls there was a good correlation (r=0.74) between the functional and immunological (ELISA) evaluation. In 123 patients with both evaluation methods but more pronounced with the measurement of the protein C activity a significant protein C deficiency was found in the patient groups with disseminated solid tumors, inflammatory diseases and myocardial infarction. Besides detection of hereditary PC deficiency Type II (generation of functionally abnormal PC) the functional assay profits by recording PC inhibitor complexes and otherwise dysfunctional PC in DIC. Thus, in patients with hematological neoplasias, only protein C activity was significantly decreases. Decrease of PC activity was more pronounced compared to PC Ag in liver disease indicating synthesis of functionally deficient PC, and in oral anticoagulant treatment due to detection of PIVKA-PC.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01745501
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  • 3
    Electronic Resource
    Electronic Resource
    Interaction of metoprolol, propranolol and atenolol with concurrent administration of cimetidine (1982)
    Springer
    Journal of molecular medicine 60 (1982), S. 1401-1407 
    Details
    ISSN: 1432-1440
    Keywords: Drug Interaction ; Cimetidine ; Metoprolol, propranolol, atenolol ; Chronic treatment ; Arzneimittelinteraktion ; Cimetidin ; Metoprolol, Propranolol, Atenolol ; Chronische Therapie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Die Pharmakokinetik von Metoprolol, Propranolol und Atenolol wurde nach jeweils 7tägiger oraler Monotherapie mit diesen Substanzen und nach 7tägiger kombinierter Gabe jedes Betablockers zusammen mit Cimetidin bei 6 gesunden Probanden geprüft. Cimetidinapplikation führte zu keiner Änderung des kinetischen Verhaltens von Atenolol. Demgegenüber stiegen nach Cimetidingabe die maximalen Metoprolol-Plasmaspiegel durchschnittlich um 70% und die von Propranolol um 95% im Vergleich zur Monotherapie mit diesen beiden Betablockern an (P〈0,05). Ähnlich verhielt sich die AUC beider Betablocker unter zusätzlicher Therapie von Cimetidin (P〈0,05). Bis auf einen geringen, jedoch nicht signifikanten Anstieg der Eliminationshalbwertzeit von Metoprolol und Propranolol bei gleichzeitiger Cimetidingabe wurden andere kinetische Parameter dieser beiden Pharmaka durch Cimetidin nicht bemerkenswert verändert. Die am 6. Tag jeder Behandlungsphase gemessene Hemmung der belastungsabhängigen Tachykardie ergab keine signifikanten Unterschiede zwischen der Monotherapie mit den jeweiligen Betablockern und deren kombinierter Gabe mit Cimetidin. Außer einem Probanden, der am 6. Tag der Therapie mit Metoprolol und Cimetidin über Angstgefühl, Schwäche und Schweißausbruch klagte, wurden weder in der Behandlungsperiode von Cimetidin mit den 3 Betablockern noch in den Monotherapiephasen Nebenwirkungen beobachtet.
    Notes: Summary Pharmacokinetics of metoprolol, propranolol, and atenolol were investigated in six healthy volunteers following 7 days of oral monotherapy with these drugs, and after 7 days concurrent administration of each of these betareceptor antagonists with cimetidine. Application of cimetidine did not lead to any interaction with atenolol, whereas mean peak plasma levels of metoprolol were increased by 70%, and those of propranolol by 95% due to concurrent administration of cimetidine (P〈0.05). The plasma level time curve (AUC) of the two above-mentioned beta blockers behaved similarly (P〈0.05). Other kinetic parameters of these two drugs were not influenced to a statistically significant extent by cimetidine, despite the tendency for the elimination half-life of metoprolol and propranolol to be prolonged when cimetidine is added. Measurement of exercise-induced tachycardia on the sixth day of administration showed no differences between monotherapy with the beta blockers and combined treatment with each of them together with cimetidine. Apart from one volunteer who complained of anxiety, weakness, and sweating on the sixth day of cimetidine/metoprolol administration, no adverse effects could be observed during the combination therapy with cimetidine and the beta blockers, nor during monotherapy with beta blockers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01716245
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  • 4
    Electronic Resource
    Electronic Resource
    Patientin mit Takayasu-Arteriitis und Protein C- sowie AT III-Mangel (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 752-756 
    Details
    ISSN: 1432-1440
    Keywords: Takayasu's arteriitis ; Protein C- ; AT III-deficiency
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A 24-year-old patient was admitted to our hospital because of vertigo, coldness and exercise-dependent pain in the left arm. She reported to have suffered from tuberculosis of the lung and a non-A-non-B hepatitis five years ago. Angiography of the aorta thoracica revealed a complete obstruction of the left arteria (a.) subclavia, stenosis of the a. carotis communis on both sides, of the a. carotis interna and the a. vertebralis on the left side as well as a non-detectable perfusion of the upper and medium segment of the left lung. ESR was elevated with 89/128 mm n.W., a hypochromic anaemia, thrombocytosis, hypalbuminaemia, elevation of alpha 2 and gammaglobulins in serum as well as a reduced quick value were found. AT III and protein C concentrations in plasma were also decreased, whereby protein C activity was reduced additionally. HLA-B-51 was positive. Takayasu's arteriitis was diagnosed by us. High-dose treatment with corticosteroids led to a considerable improvement of the clinical status and laboratory parameters of the patient. As this therapy was not associated with a normalization of protein C and AT III concentrations in plasma, protein C and AT III deficiency could be of significance in the development of Takayasu's arteriitis. Until now protein C and AT III deficiency were not described in patients with Takayasu's arteriitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01736813
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  • 5
    Electronic Resource
    Electronic Resource
    Lupus anticoagulant associated syndrome in benign and malignant systemic disease — Analysis of ten observations (1987)
    Springer
    Journal of molecular medicine 65 (1987), S. 852-859 
    Details
    ISSN: 1432-1440
    Keywords: Lupus anticoagulant ; Paraproteinemia ; Systemic lupus erythematosus ; Multiple myeloma ; Lymphoproliferative diseases ; Lymphoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leucocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms. Since the clinical syndrome associated with the lupus anticoagulant in patients with autoimmune disorders has been proposed to arise from the action of autoantibodies against phospholipids, it is attractive to hypothesize that the findings in the patients with malignant diseases were caused by an autoantibody activity of the monoclonal immunoglobulin. This assumption is substantiated by the observation that in one patient the paraprotein level correlated with the prolongation of the coagulation times and the severeness of the clinical perturbations. Although paraproteins mimicking the laboratory alterations of the lupus anticoagulant have been reported before, the corresponding clinical features have not yet been described in malignant monoclonal gammopathies. The syndrome may be juxtaposed to other systemic disorders complicating paraproteinemias, and is possibly more frequent than is as yet known.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01737004
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  • 6
    Electronic Resource
    Electronic Resource
    Dosierung und Elimination von Dextran 40 bei Hämodialysepatienten (1975)
    Springer
    Journal of molecular medicine 53 (1975), S. 523-527 
    Details
    ISSN: 1432-1440
    Keywords: Dextran 40 ; elimination ; dosage ; hemodialysis ; bleeding ; Dextran 40 ; Elimination ; Dosierung ; Hämodialyse ; Blutungen
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei 24 Hämodialysepatienten wurden nach einmaliger und wiederholter Gabe von Dextran 40 (Rheomacrodex®) die Dextranspiegel im Serum bestimmt und daraus die Eliminationshalbwertzeiten errechnet. Diese betrugen bei Heimdialysepatienten 2237±447 min, bei Zentrumsdialysepatienten 4283±810 min und waren damit gegenüber nierengesunden Patienten (HWZ=573±183 min) auf das Fünf- bzw. Zehnfache verlängert. Die Unterschiede zwischen Heimdialyse- und Zentrumsdialysepatienten erklären sich durch die bessere Nierenrestfunktion der ersteren. Während der Hämodialyse kam es zu keinem Abfall der Dextranspiegel i.S. Weiterhin zeigte sich, daß die exponentielle Elimination von Dextran 40 über einen Beobachtungszeitraum von 6,25 Tagen durch die intermittierende Hämodialyse nicht beeinflußt wurde. Da keine nennenswerte Ausscheidung von Dextran 40 durch die Hämodialyse erfolgt, braucht die intermittierende Hämodialyse bei der Dosierung nicht berücksichtigt zu werden. Die Dosierung von Dextran 40 hat sich jedoch streng nach der verlängerten Eliminationshalbwertzeit zu richten. Die Gabe von 2 × 50 g Dextran 40 pro Woche (2 × 500 ml 10%iges Dextran 40) kann schon nach der 4. Infusion zu Dextranspiegeln i.S. über 20 g/l und zu Blutungen führen. Um diese Komplikationen zu vermeiden, wird eine von der Nierenfunktion unabhängige Initialdosis vorgeschlagen mit einer anschließenden Erhaltungsdosis, die sich nach der Nierenfunktion richtet.
    Notes: Summary In 24 patients on regular hemodialysis the serum levels and the half-life of dextran 40 were determined after single or repeated infusion of dextran 40 (Rheomacrodex®). One group of hemodialysis trainees had a dextran 40 half-life of 2237±447 min. In contrast, a second group, consisting of hospital dialysis patients, had a dextran 40 half-life of 4283±810 min, whereas patients with normal renal function had a half-life of 573±183 min. The difference in dextran half-life between the two groups of hemodialysis patients may be explained by the better residual ronal function of our hemodialysis trainees. During hemodialysis no change in serum dextran levels could be observed. Intermittent hemodialysis, also, had no influence on the exponential elimination of dextran over a period of 6.25 days. Since hemodialysis by itself has no effect upon dextran elimination, the dosage of dextran 40 has to be adjusted to the prolonged elimination time only, disregarding dialysis. After the fourth infusion of 50 g dextran 40 (twice a week 500 ml of 10% dextran 40) serum dextran levels exceeding 20 g/l and cutaneous bleeding were observed. To avoid these complications an initial saturation dose is suggested, followed by a maintenance dose adjusted to the impaired renal function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468757
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  • 7
    Electronic Resource
    Electronic Resource
    Volumenzweiteffekt nach einmaliger Infusion von Hydroxyäthylstärke (1978)
    Springer
    Journal of molecular medicine 56 (1978), S. 977-983 
    Details
    ISSN: 1432-1440
    Keywords: Hydroxyethyl starch ; Molecular weight ; Plasma volume ; Serum amylase ; Hydroxyäthylstärke ; Molekulargewicht ; Plasmavolumen ; Serumamylase
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 6 Patienten ohne Anhalt für eine Nieren-, Leber- oder Pankreaserkrankung erhielten innerhalb von 60 min 500 ml 6% Hydroxyäthylstärke 450/0,7. Während der Infusion stieg das Plasmavolumen von 2,72±0,101 auf 3,36±0,141 an, fiel in der 2. Stunde wieder auf 3,02±0,101 ab und erreichte nach der 4. Stunde einen zweiten Gipfel von 3,23±0,121 (p〈0,01). Nach 24h lag das Plasmavolumen noch 4,8% über dem Ausgangswert. Dieser „Volumenzweiteffekt“ ist nicht durch die Hydroxyäthylstärke-Gesamtkonzentration zu erklären, da diese kontinuierlich exponentiell abfiel. Mit dem erneuten Volumenanstieg nach der 4. Stunde ging eine Abnahme des Zahlenmittels004Dn und des Gewichtsmittels004Dw einher. Dies spricht dafür, daß infolge der Fraktionierung durch die Serumamylase vermehrt osmotisch aktive Hydroxyäthylstärke-Moleküle entstehen, die zu einer Zunahme des Plasmavolumens führen. 12–24h nach Infusionsbeginn stieg die Serumamylase auf über das Doppelte ihres Ausgangswertes an. Ursache dieser Hyperamylasämieist die Bildung eines Hydroxyäthylstärke-Amylase-Komplexes, der infolge seiner Größe nur schwer eliminiert wird. Um eine Volumenüberlastung zu vermeiden, muß bei mehrmaliger Infusion von Hydroxyäthylstärke der Volumenzweiteffekt berücksichtigt werden, besonders bei Patienten nit eingeschränkter kardialer Leistungsbreite.
    Notes: Summary 6 patients without evidence for renal, hepatic or pancreatic disease were treated with intravenous infusions of 500 ml hydroxyethyl starch (6%) over a period of 60 min. In the course of the infusion we observed an increase in plasma volume from 2.72±0.101 to 3.36±0.141. After 2h plasma volume decreased to 3.02±0.101 but showed a second peak of 3.23±0.121 after 4h (p〈0.01). 24h following infusion an increase in plasma volume of 4,8% was found as compared to preinfusion values. The second increase in plasma volume cannot be explained by the total concentration of hydroxyethyl starch since the latter decreased continuously. The increase in plasma volume was accompanied by a decrease in average molecular weight004Dw and004Dn. It is suggested that serum amylase produces small osmotic active molecules by degradation of hydroxyethyl starch, thus leading to an increase in plasma volume. 12–24h after the infusion of hydroxyethyl starch serum amylase was more than twice as high basal values. This is caused by the formation of a high molecular hydroxyethyl starch-amylase-complex which cannot be eliminated easily. When hydroxyethyl starch is given repeatedly to normovolemic patients, the second increase in plasma volume should be considered as a possible cause for acute hypervolemia. This is especially true for patients with myocardial insufficiency.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01480153
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  • 8
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and safety of propiverine in patients with fatty liver disease (1998)
    Springer
    European journal of clinical pharmacology 54 (1998), S. 767-771 
    Details
    ISSN: 1432-1041
    Keywords: Key words Propiverine ; Fatty liver disease ; Pharmacokinetics ; Adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: The present study was designed to assess the pharmacokinetics of propiverine after single and multiple dosing in patients with and without fatty liver disease. Methods: The serum concentration-time curves of propiverine and its main metabolite propiverine-N-oxide were investigated in 12 patients with mild to moderate impairment of liver function (mean antipyrine clearance 26.0 ml · min−1) and in 12 controls (antipyrine clearance 42.8 ml · min−1). Subjects were treated orally with propiverine hydrochloride (Mictonorm) for 5 days (15 mg t. i. d.) to reach steady state. Results: No significant differences were observed for propiverine and its main metabolite with regard to peak serum concentration (Cmax), area under the serum concentration-time curve (AUC) and elimination half-life (t1/2). Adverse events were reported by 12 patients. Five patients with fatty liver disease and seven patients with normal liver function complained of dry mouth and/or blurred vision. All adverse events reported were transient and mild. Conclusion: No pharmacokinetic differences relevant for safety were observed, comparing patients with and without fatty liver disease following repeated oral administration of propiverine. Thus there seems to be no need to adjust the dose in patients with mild to moderate impairment of liver function.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050549
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  • 9
    Electronic Resource
    Electronic Resource
    Drug information services: initial experiences in Dresden (1998)
    Springer
    European journal of clinical pharmacology 54 (1998), S. 667-668 
    Details
    ISSN: 1432-1041
    Keywords: Key words Drug Information Centre ; Primary healthcare
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002280050532
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  • 10
    Electronic Resource
    Electronic Resource
    Elimination of hexamethylene diisocyanate cross-linked polypeptides in patients with normal or impaired renal function (1978)
    Springer
    European journal of clinical pharmacology 14 (1978), S. 405-412 
    Details
    ISSN: 1432-1041
    Keywords: Colloidal plasma substitutes ; cross-linked polypeptides ; Haemaccel® ; pharmacokinetics ; renal failure
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Infusions of 3.5% isocyanate cross-linked polypeptide solution 500 ml were given to 52 patients with normal or impaired renal function: glomerular filtration rate (GFR)=0–133 ml/min. The serum concentration and urinary excretion of hydroxyproline were measured and the equivalent polypeptide concentrations were calculated from the results. In patients with normal renal function (GFR〉90 ml/min) the proportion of polypeptide excreted in the urine up to 12 h was 45.4±2.6% ( $$\bar X$$ ±SEM), up to 24 h 47.7±2.9% and up to 48 h 49.3±3.4%. In patients with moderate renal insufficiency (GFR=30–90 ml/min) there was no decrease in polypeptide excretion and even in patients with more serious impairment of GFR (11–30 ml/min) 48-h urinary polypeptide excretion was still 40.6±5.9%. In patients with GFR of 2–10 ml/min polypeptide excretion fell to 10.7±3.2% during the first 12 h, although there was an increase in later collection periods as compared to patients with normal renal function −19.9±3.9% in 24 h and 27.0±3.5% in 48 h. The elimination half-life (t1/2) calculated from serum concentrations was 505±30 min ( $$\bar X$$ ±SEM) in patients with normal renal function (GFR〉90 ml/min). Only when the GFR fell below 30 ml/min did it slowly begin to increase. In patients with minimal residual renal function (GFR=0–0.5 ml/min), who were on haemodialysis, the elimination half-life was 985±49 min, i.e. approximately twice the normal. Twice weekly infusion of 3.5% polypeptide solution 500 ml over a period of 6 weeks did not produce any significant cumulation in haemodialysis patients (GFR=0–0.5 ml/min). A weekly dose of polypeptide 35 g appeared to be quite safe when given for several weeks, even to anuric patients. As no significant amount of polypeptide was lost during haemodialysis, the dose can be chosen without taking into account any effect of intermittent haemodialysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00716381
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