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  • 1
    Electronic Resource
    Electronic Resource
    The inhibition of drug metabolism by cimetidine in patients with liver cirrhosis (1984)
    Springer
    Journal of molecular medicine 62 (1984), S. 1126-1131 
    Details
    ISSN: 1432-1440
    Keywords: Cimetidine ; Liver cirrhosis ; Theophylline ; Drug metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effect of cimetidine treatment, 1 g daily over 6 days, on the disposition of theophylline was studied in nine patients with liver cirrhosis and in nine patients without liver disease. Plasma elimination half-life tended to increase from 14.6±8.2 h to 24.3±14.1 h in the cirrhotic patients (P〉0.05) and from 8.3±4.2 h to 10.3±4.1 h in the control patients (P〈0.05). Total plasma clearance decreased from 0.50±0.23 ml/kg/min to 0.41±0.21 ml/kg/min (P〈0.05) in the cirrhotics and from 0.77±0.34 ml/kg/min to 0.58±0.18 ml/kg/min (P〈0.05) in the controls. Pretreatment clearance values were also significantly reduced in the cirrhosis group. No change was observed in the volume of distribution of theophylline. The degree of inhibition of theophylline metabolism did not depend on whether the patients were smokers, or whether they had low pretreatment clearance values. In liver cirrhosis, inhibition of drug metabolism by cimetidine varies widely and is unpredictable in the individual patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01782470
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  • 2
    Electronic Resource
    Electronic Resource
    Hans Dengler zum 60. Geburtstag (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 1137-1138 
    Details
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740588
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  • 3
    Electronic Resource
    Electronic Resource
    Factors predicting the therapeutic outcome of duodenal ulcer treatment with H2-receptor antagonists (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 1152-1159 
    Details
    ISSN: 1432-1440
    Keywords: Duodenal ulcer healing ; Acid secretion ; Cimetidine pharmacokinetics ; Treatment response
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In a prospective trial 37 duodenal ulcer patients were treated daily with 1 g cimetidine. Personal and clinical data were obtained for all patients, acid secretion studies performed before and during treatment, and pharmacokinetic parameters of cimetidine determined. The healing rate after 4 weeks was 64.9% (24 patients). Non-Responders included a higher proportion of smokers, patients with a history of ulcer and previous treatment with H2-receptor antagonists than Responders. Basal acid output (BAO) and peak acid output (PAO) values were not different between the two groups, nor was the reduction of BAO and PAO under cimetidine. However, more Responders had complete suppression of BAO than Non-Responders. A correlation existed in both groups between cimetidine plasma concentration and PAO suppression but not with BAO suppression. Regular drug intake (compliance) was found in about 90% in both groups. Cimetidine bioavailability parameters were identical in both groups, but Non-Responders had a higher peak concentration and a shorter time of peak concentration. Discriminant analysis enabled a prediction of treatment response in 89.2% of the patients by using five factors: time of peak concentration of cimetidine, previous H2-receptorantagonist treatment, peak concentration, smoking, and alcohol use. Prediction of treatment response is increased by use of drug related variables.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01740590
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  • 4
    Electronic Resource
    Electronic Resource
    Serum-cholesterol-lowering effect of metronidazole and possible mechanisms of action (1985)
    Springer
    Journal of molecular medicine 63 (1985), S. 279-281 
    Details
    ISSN: 1432-1440
    Keywords: Metronidazole ; Bile acids ; Cholesterol absorption ; Serum cholesterol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In five patients with Crohn's disease long-term therapy with metronidazole (400 mg b.i.d.) was followed by a significant reduction of total serum cholesterol from 179 mg/dl to 156 mg/dl, 134 mg/dl, and 143 mg/dl, after 2–4 months, 6 months, and 9–12 months, respectively. Lipoprotein analysis before and after 3 weeks of administration of metronidazol (400 mg/day) to five normolipemic volunteers revealed that LDL-cholesterol was reduced by 21% (P〈0.05), whereas HDL-cholesterol remained unchanged. Biliary secretion of cholesterol and bile acids were reduced by 13% and 20% (P〈0.05), respectively, which might suggest a decreased sterol synthesis. The amount and percentage of intestinal cholesterol absorption were decreased by 33% and 22% (P〈0.05). Thus, a possible decrease in sterol synthesis and a reduction of cholesterol absorption might be responsible for the serum-cholesterol-lowering effect of metronidazole. However, caution should be taken when considering metronidazole for long-term treatment of patients with hypercholesterolemia due to possible side effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01731475
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  • 5
    Electronic Resource
    Electronic Resource
    Arzneimittelinteraktionen mit oralen Antikoagulantien vom Cumarintyp (1973)
    Springer
    Journal of molecular medicine 51 (1973), S. 1081-1090 
    Details
    ISSN: 1432-1440
    Keywords: Anticoagulants ; coumarins ; drug interaction ; protein binding ; enzyme induction ; enzyme inhibition ; Antikoagulantien ; Cumarine ; Arneimittelwechselwirkung ; Interaktion ; Eiweißbindung ; Enzyminduktion ; Enzymhemmung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Eine große Zahl von Medikamenten tritt bei gleichzeitiger Gabe in Interaktion mit Cumarinderivaten. Wesentliche Mechanismen sind dabei Resorptionshemmung, Verdrängung aus der Plasmaeiweißbindung, Hemmung oder Induktion des metabolisierenden Enzymsystems sowie Beeinflussung von Synthese oder Abbau der Vitamin Kabhängigen Gerinnungsfaktoren. Auch die Cumarine selbst sind in der Lage, die Metabolisierung anderer Pharmaka hemmend zu beeinflussen. Es ergibt sich die Notwendigkeit, neu einzuführende Medikamente auf die Interaktion mit Cumarinen zu testen. Eine sorgfältige Überwachung des Patienten ist bei Beginn oder Beendigung jeder Therapie mit einem in Kombination mit Cumarinen eingesetzten Pharmakon angezeigt.
    Notes: Summary Many drugs are known to modify the pharmacological action of coumarin anticoagulants when administered simultaneously. Mechanisms of interaction may consist in inhibition of absorption, displacement from protein binding sites, inhibition or induction of drug metabolizing enzymes in liver microsomes, and effect on synthesis and metabolization of the vitamin K-dependent clotting factors. Coumarins also may inhibit the metabolic degradation of other drugs. It is therefore necessary to test new compounds for a possible interaction with coumarin agents. Patients treated with coumarin anticoagulants should be controled carefully for changes in the hypoprothrombinaemic action when additional drugs are given or when these are discontinued.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01468301
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  • 6
    Electronic Resource
    Electronic Resource
    Untersuchungen über die Magensaftsekretion nach Stimulation mit Pentagastrin (ICI 50 123) (1968)
    Springer
    Journal of molecular medicine 46 (1968), S. 93-97 
    Details
    ISSN: 1432-1440
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In two normal subjects and ten patients the gastric secretory response to pentagastrin has been determinated. Pentagastrin is a synthetic polypeptide with an aminoacid sequence equal to that of the biologically active component of human gastrin. After intravenous application, a dose responcee relationship has been established between pentagastrin and gastric acid secretion over a range of 0,6 to 6,0γ/kg/hr of the polypeptide. As anticipated, both electrolyte composition and secretory volume change depending on the acid concentration. Subcutanously administered pentagastrin stimulated acid secretion with a correlation to time similar to that after histamine injection. The acid secretory capacity of pentagastrin reaches an average of 89% of that of 1.5 mg/kg of histolog showing, in single cases, a different relation to the histolog response. Only negligible side effects, as nausea and vomiting, have been observed after intravenous injection of pentagastrin. When pentagastrin was given subcutanously side effects, were more pronounced in a few cases, but temporary.
    Notes: Zusammenfassung Die Einwirkung von Pentagastrin, einem Pentapeptid, welches aus der biologisch wirksamen Aminosäuresequenz des menschlichen Gastrins besteht, auf die Magensaftsekretion wurde bei 2 Normalpersonen und 10 Patienten untersucht. Bei intravenöser Verabreichung besteht in einem Bereich von 6,0–0,6γ/kg/h eine Dosis-Wirkungs-Beziehung zwischen Pentagastrin und Säuresekretion. Die Elektrolytzusammensetzung des Magensaftes und das Sekretionsvolumen verändern sich erwartungsgemäß in Abhängigkeit von der Säurekonzentration. Pentagastrin subcutan verabreicht, verursacht eine Säuresekretion, deren zeitlicher Ablauf der Säuresekretion nach Histamin ähnlich ist. Die Säuresekretionsleistung nach Pentagastrin beträgt im Durchschnitt 89% der Säuresekretion nach subcutaner Belastung mit 1,5 mg je Kilogramm Histalog, zu der sie in Einzelfällen größere Unterschiede aufweist. Die Nebenwirkungen in Form von Übelkeit und Brechreiz waren bei intravenöser Verabreichung nur in Einzelfällen stärker und klangen rasch ab.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01747475
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  • 7
    Electronic Resource
    Electronic Resource
    Malignant pheochromocytoma. Effect of oral α-methyl-p-tyrosine upon catecholamine metabolism (1979)
    Springer
    Journal of molecular medicine 57 (1979), S. 351-355 
    Details
    ISSN: 1432-1440
    Keywords: Malignes Phäochromocytom ; Behandlung ; α-Methyl-p-Tyrosin ; Catecholamin-Metabolismus ; Malignant Pheochromocytoma ; Treatment ; α-methyl-p-tyrosine ; Catecholamine Metabolism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary In a patient with malignant pheochromocytoma treated unsuccessfully with propranolol and phenoxybenzamine the additional therapy with α-methyl-p-tyrosine resulted in a substantial decrease of the blood pressure to almost normal values. His general condition improved considerably. During therapy the urinary excretion rates of catecholamines and all their metabolites dropped to about 50% of control values. O-Hydroxylation of α-methyl-p-tyrosine could be demonstrated by the isolation of α-methyldopa and α-methylnormetanephrine. After discontinuation of treatment with α-methyl-p-tyrosine blood pressure and catecholamines returned to control values within two days.
    Notes: Zusammenfassung Bei einem Patienten mit malignem Phäochromocytom führte die Behandlung mit α-methyl-p-Tyrosin zu einer fast vollständigen Normalisierung des Blutdrucks. Propranolol und Phenoxy-benzamin waren vorher ohne großen Erfolg angewendet worden. Das Allgemeinbefinden des Patienten besserte sich beträchtlich. Während der Behandlung fielen die Ausscheidungsraten von Catecholaminen und ihren Metaboliten auf ca. 50% der Werte vor Behandlung ab. Der Nachweis von α-Methyldopa und α-Methylnormetanephrin bewies die Möglichkeit der o-Hydroxylierung von α-methyl-p-Tyrosin. Nach Beendigung der Behandlung stiegen Blutdruckwerte und Ausscheidung von Catecholaminen innerhalb von 2 Tagen wieder in die vor Behandlung gefundenen hochpathologischen Bereiche an.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01476565
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  • 8
    Electronic Resource
    Electronic Resource
    Diphenylhydantoin: Correlation between protein binding and albumin concentration (1975)
    Springer
    Journal of molecular medicine 53 (1975), S. 445-446 
    Details
    ISSN: 1432-1440
    Keywords: Diphenylhydantoin ; Eiweißbindung ; Albuminkonzentration ; nephrotisches Syndrom ; Diphenylhydantoin ; protein binding ; albumin concentration ; nephrotic syndrome
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The unbound fraction of diphenylhydantoin is inversely correlated with the patient's serum albumin concentration and can be accurately estimated graphically without binding analyses. The data for this relationship was obtained from a study in which we observed that the unbound fraction of diphenylhydantoin was two times higher in patients with the nephrotic syndrome. However, in these patients it was not necessary to diminish the dosage since the absolute concentration of unbound drug was unchanged due to a compensatory increase in the apparent volume of distribution and plasma clearance.
    Notes: Zusammenfassung Es besteht eine negative Korrelation zwischen dem nichtgebundenen Anteil an Diphenylhydantoin und der Albuminkonzentration im Plasma des Patienten. Aus dieser Relation kann die Eiweißbindung ohne spezielle Bindungsstudien graphisch bestimmt werden. Die Ergebnisse hierzu wurden aus einer Untersuchung erhalten, in der bei Patienten mit nephrotischem Syndrom ein auf das Doppelte erhöhter Anteil an nichtgebundenem Diphenylhydantoin beobachtet wurde. Eine Dosisreduktion war bei diesen Patienten jedoch nicht erforderlich, da die absolute Konzentration des nichtgebundenen Medikamentes als Folge einer Erhöhung des Verteilungsvolumens und der Plasma-Clearance nicht erhöht war.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01493371
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  • 9
    Electronic Resource
    Electronic Resource
    Cimetidine pharmacokinetics and dosage requirements in children (1985)
    Springer
    European journal of pediatrics 144 (1985), S. 72-76 
    Details
    ISSN: 1432-1076
    Keywords: Cimetidine ; Children ; Pharmacokinetics ; Halflife ; Clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of cimetidine (10 mg/kg) were investigated in 11 children following an oral dose and in 9 children following an intravenous dose. The children ranged in age from 4–13 years and were undergoing radiology for upper gastrointestinal tract pain. Compared with a group of adults, the children had a higher total body clearance (11.6±3.4 versus 7.0±2.5 ml/min per kg; P〈0.005), a larger apparent volume of distribution (1.24±0.40 versus 0.80±0.24 l/kg; P〈0.005) and a shorter elimination half-life (83±26 versus 122±16 min; P〈0.001) of cimetidine. Renal clearance in children comprised 70% of total body clearance, more than double that of adults (9.0±1.9 versus 4.2±2.1 ml/min per kg; P〈0.001). The area under the cimetidine plasma concentration: time curve after the oral dose was on average 42% in children compared with adults. The mechanism for the increased elimination of cimetidine in children is suggested to be an increase in the renal tubular secretory transport of cimetidine in the kidney. A statistically significant negative correlatio was observed between age and cimetidine renal clearance. A cimetidine dosage regimen of approximately 30 mg/kg per day in three to four divided doses would be an appropriate dose in children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00491931
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  • 10
    Electronic Resource
    Electronic Resource
    Single and multiple dose pharmacokinetics of pindolol (1978)
    Springer
    European journal of clinical pharmacology 13 (1978), S. 13-16 
    Details
    ISSN: 1432-1041
    Keywords: Pharmacokinetics ; beta-blocking drugs ; pindolol ; propranolol ; multiple doses ; steady state concentration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of pindolol were studied in six healthy individuals following a single 10 mg dose (SD) and multiple (5 mg tid over 6 days) doses (MD). The plasma elimination half-life was identical after SD (4.7±0,8 h) and MD (4.1±1.1 h). Steady state plasma concentrations were reached after 36 h and remained stable thereafter. The variation in steady state concentrations was small in each individual and also between individuals. The steady state concentration of pindolol can be predicted from the pharmacokinetic data obtained after a single dose. The results of the present study suggest that the disposition of pindolol is linear over the concentration range studied.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00606675
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