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  • 1
    ISSN: 0920-9964
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 17 (1980), S. 275-284 
    ISSN: 1432-1041
    Keywords: chlormethiazole ; cirrhosis of the liver ; antipyrine ; protein binding ; pharmacokinetics ; healthy volunteers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of chlormethiazole after oral and intravenous administration was studied in six healthy volunteers and eight patients with alcoholic cirrhosis of the liver. Plasma concentration-time curve after the intravenous infusion could adequately be described by two- or three-compartment open models both in healthy volunteers and in the patients. Based on the areas under the plasma concentration-time curves, the systemic bioavailability of oral chlormethiazole was about ten times greater in the patients than in healthy controls. The elimination of chlormethiazole was relatively less retarded in the patients, as indicated by a decrease of about 30% in its plasma clearance. In the patients the plasma protein binding of chlormethiazole was decreased, but the volume of distribution and half-life of elimination were unchanged. The increase in bioavailability of chlormethiazole was associated with significant alteration in the serum levels of bilirubin, albumin, alkaline phosphatase, prothrombin-proconvertin activity (P + P) and elimination rate of antipyrine or14C-aminopyrine. The increased bioavailability of oral chlormethiazole was due to impaired first-pass metabolism in the cirrhotic liver. A considerable reduction in dose seems to be indicated if oral chlormethiazole is used in patients with advanced cirrhosis of the liver. A substantial fraction of dose, averaging 15%, was lost during the intravenous infusion, presumably due to adsorption to the infusion tubing.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 20 (1981), S. 123-125 
    ISSN: 1432-1041
    Keywords: paracetamol ; breast milk ; plasma ; drug excretion in breast milk ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Breast milk and plasma levels of paracetamol were monitored in 3 lactating women after ingestion of a single 500 mg dose of paracetamol. The paracetamol concentrations were consistently lower in milk, with a mean milk/plasma AUC ratio of 0.76. This value was in close agreement with the milk/plasma partition ratio of 0.81 foundin vitro, and could be related to quantitative binding differences between the two fluids. The half-lives of paracetamol in plasma and breast milk were almost identical, with an overall mean of 2.7 h. As less than 0.1% of the maternal dose would be present in 100 ml milk, breast feeding need not be discontinued due to paracetamol treatment in conventional dosage.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0920-9964
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    BJOG 86 (1979), S. 0 
    ISSN: 1471-0528
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Four mothers receiving chlormethiazole for pre-eclampsia and their babies were the subjects of the investigation. Blood samples at delivery and blood and breast milk samples in the postpartum period were analysed for chlormethiazole. Concentrations ranged from 1·340 to 1·640 ug/g of sample in umbilical artery blood at birth, and fell to 0·010 to 0·153 ug/g in capillary blood 20 to 26 hours later. After the start of breast feeding, chlormethiazole in the babies was detectable in only 3 out of 27 serial blood samples and was 0·018, 0·009 and 0·006 μg/g. The highest calculated amount of chlormethiazole ingested at a breast feed was 37.2 ug. It is suggested that breast feeding should not be delayed solely on account of chlormethiazole therapy.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 55 (1999), S. 619-624 
    ISSN: 1432-1041
    Keywords: Key words Computerised electrocardiogram ; Heart rate changes ; Influence of food
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Objective: To study the influence of food intake on electrocardiogram (ECG) variables (heart rate, QT-, QTc-, PR-intervals, QRS-time) and morphological alterations of the T-waves in 12 healthy male volunteers. Methods: The study was of open, three-period crossover design. On each occasion, all subjects fasted from midnight. During two of the study periods, the subjects were given a standardised meal at 1.5 h and 5.5 h after the baseline assessments, respectively, whereas, during the third period, they remained fasting for the entire study period of about 9 h. ECG and blood pressure were recorded at baseline and thereafter every hour for 8 h. Results: No ECG changes were observed following the fasting condition, whereas a clear change in ECG and an increased heart rate were recorded in response to the meal intake during the other two periods. The most prominent ECG effect was the change in the size and shape of the T-waves, which were described as flattened to biphasic and, occasionally, negative. These alterations were most pronounced in the precordial leads V4 to V6 in the ECG recording immediately following the meal intake, with a gradual return to baseline conditions over 4–5 h. Moreover, a transient increase of supine systolic blood pressure was also recorded in response to the meal intake. Conclusions: The intake of a meal can cause clear and consistent ECG changes in healthy male subjects, comprising increases in heart rate as well as alterations in the size and shape of the T-waves (flattened to biphasic and, occasionally, negative). Also, a post-meal increase in the supine systolic blood pressure was recorded.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: Endogenous depression ; Desipramine ; Zimehdine ; 5-Hydroxytryptamine ; Noradrenaline ; Uptake inhibition ; Platelets ; Cerebrospinal fluid ; Monoamine metabolites
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selective inhibitors of neuronal 5-hydroxytryptamine (5-HT) and noradrenaline (NA) uptake, zimelidine and desipramine, were compared in a double blind crossover study of 40 inpatients with endogenous depression. The clinical effects of these two drugs and some biochemical variables related to the monoamine systems were studied during 4 weeks' treatment. Patients with a low pretreatment level of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) (〈20 ng/ml) responded significantly better to zimelidine treatment than those with a high pretreatment level (〉20 ng/ml). In the group treated with desipramine no difference in therapeutic outcome was obtained between patients with low and high pretreatments levels of 5-HIAA in the CSF. Attempts to correlate the steady state plasma concentrations of zimelidine, norzimelidine and desipramine with the therapeutic effect were unsuccessful. The plasma concentration of norzimelidine demonstrated a singificant (P〈0.05) positive correlation with age. The mean value of the uptake of 14C-5-HT in the patients' platelets, when measured before the treatment, was significantly (P〈0.05) lower than found in a control group. Zimelidine, mainly via its metabolite norzimelidine, caused a pronounced inhibition of uptake of 14C-5-HT in platelets, decrease in whole blood 5-HT and inhibition of accumulation of 14C-5-HT in rat hypothalamic synaptosomes incubated in the patients plasma. Desipramine produced a slight inhibition of accumulation of 14C-5-HT in rat synaptosomes, but a marked inhibition of uptake of 14C-5-HT in the patient's platelets and a decrease in whole blood 5-HT. The accumulation of 3H-NA in rat synaptosomes incubated in the patients' plasma was strongly inhibited by desipramine treatment but only slighty affected by zimelidine.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2072
    Keywords: Senile dementia ; Alzheimers disease ; Alaproclate ; Pharmacokinetics ; 5-Hydroxytryptamine ; Uptake inhibition ; Monoamine metabolites ; Cerebrospinal fluid
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Alaproclate, a specific inhibitor of neuronal serotonin re-uptake, was given to 12 patients with dementia of Alzheimer type. The drug was rapidly absorbed and an elimination half-life of 7.1±0.9 h (± SD, n=8) was calculated. Plasma protein binding for alaproclate was 82 ±1%. Two weeks of repeated administration produced plasma concentrations of alaproclate similar to those predicted from a single dose. The pharmacological effect of the drug was demonstrated by an inhibition of serotonin uptake in the patients' platelets and a reduction of the serotonin concentration in blood. Global rating of clinical efficacy showed a positive effect of alaproclate in five of the patients, mainly regarding emotional functions.
    Type of Medium: Electronic Resource
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