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  • 1
    ISSN: 1432-1041
    Keywords: Furosemide ; renal transplant recipients ; kidney donors ; naproxen ; dehydration ; pharmacokinetics ; salt-regulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The response to 40 mg furosemide p.o. in 6 healthy kidney donors and 6 renal transplant recipients with and without naproxen pretreatment has been studied. No volume replacement was given in order to study the development of tolerance. The subjects showed an average dehydration of 1.5 kg · 6 h−1. While mean creatinine clearance was equal in patients and donors (76 vs 80 ml/min), renal furosemide clearance was significantly lower in the patients (47 vs 81 ml/min; P〈0.05). The patients also excreted a smaller fraction of the dose in the urine (5.7 vs 7.8 mg/6 h; P〈0.05). As the overall renal sensitivity was similar in the two groups, the natriuretic response was correspondingly smaller in transplant recipients as compared to donors. Within the observation period of 6 h after dosing, acute tolerance developed in the donors and in 4 of the 6 patients, as shown by clockwise hysteresis in the dose (urine furosemide excretion rate)-response (natriuresis) curves. Pretreatment with naproxen reduced renal sensitivity to furosemide (right shift of the dose response curve) in all the donors but in only 2 of the patients. In both groups acute tolerance was less pronounced after naproxen, which may indicate involvement of the prostaglandin system in the development of acute tolerance. The results may also indicate regeneration of sympathetic nerves with functional capacity in at least some renal transplants, or that other mechanisms of salt regulation compensate for loss of sympathetic nerve activity.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 26 (1984), S. 197-207 
    ISSN: 1432-1041
    Keywords: furosemide ; bioavailability ; pharmacokinetics ; oral administration ; i.v. administration ; drug absorption ; moment analysis ; food effect ; dissolution effect
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Furosemide 40 mg was administered to 8 healthy subjects as an i.v. bolus dose, as 1 tablet in the fasting state, and as 1 tablet and a solution after food intake. The i.v. data gave a total body clearance of 162±10.8 ml/min and a renal clearance of 117±11.3 ml/min; the volume of distribution at steady state was 8.3±0.61. Oral administration gave a bioavailability of the tablet (fasting) of 51%. Food intake slightly reduced the bioavailability, but not to a significant extent. There was no significant difference in availability between the tablet and the solution. Moment analysis gave a mean residence time after the i.v. dose, MRTi.v., of 51±1.5 min. The mean absorption times (MAT) for all oral doses were significantly longer than the MRTi.v., indicating absorption rate-limited kinetics of furosemide. On average, food delayed the absorption by 60 min. The MAT for the tablet in the postprandial state was significantly longer than for the solution, indicating dissolution rate-limited absorption of the tablet.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 37 (1989), S. 173-180 
    ISSN: 1432-1041
    Keywords: frusemide ; nephrotic syndrome ; albumin ; dextran ; pharmacokinetics ; renin-angiotensin-aldosterone system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The renal handling and effects of an intravenous bolus of frusemide with and without plasma volume expansion with dextran or albumin, and with large variations in plasma albumin concentration, have been studied in five patients with the nephrotic syndrome. Decreased renal sensitivity to frusemide was found in only one patient, who also had hypovolaemia and an activated renin-angiotensin-aldosterone system. Plasma volume expansion increased the diuresis but not the saluresis, and slightly increased renal sensitivity to frusemide. An increase in albuminuria after albumin infusion did not reduce the sensitivity to frusemide. A decrease in plasma albumin concentration from 33 g·l−1 after albumin infusion to 23 g·l−1 after infusion of dextran caused a substantial increase in the renal clearance (from 84 to 123 ml·min−1), non-renal clearance (from 72 to 138 ml·min−1), and apparent volume of distribution (from 13 to 23 l) of frusemide, probably as a consequence of an increase in the unbound fraction. The rate of urinary excretion of frusemide was highest after albumin infusion, despite the fact that its renal clearance was lowest then.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: trimethoprim ; concentration ; urinary excretion ; healthy volunteers ; steady state ; pharmacokinetics ; serum creatinine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The steady state pharmacokinetics of trimethoprim was determined after 300 mg orally once daily to 6 healty volunteers for 9 days. The microbiological assay of plasma level was unreliable at trimethoprim concentrations 〉4 µg/ml, so results from an HPLC-assay are given. Steady state was present after 3 days. The plasma concentration peaked 1 to 4 h (mean 2.0 h) after the dose at a mean of 6.0 µg/ml (range 3.1–9.5 µg/ml); the minimum value was 1.5 µg/ml (range 0.6–2.9 µg/ml). The mean AUCss was 77 µg/ml · h and the mean plasma clearancess was 67 and 74 ml/min on Days 8 and 9. Renal clearance was about 60% of the plasma clearance. The average plasma half life was 10.6 h (range 8.7–15.3 h). Thus, there was considerable interindividual variation in all pharmacokinetic parameters. 72 h after the last dose trimethoprim was detectable in plasma in only 1 of the 6 subjects. The minimum urinary concentration of trimethoprim during treatment was always well above (range 22 to 220 µg/ml) the MIC values for most urinary tract pathogens. Therefore, a daily dose of 300 mg trimethoprim results in a therapeutic concentration in urine at steady state that lasts throughout the dosing interval and in most subjects probably lasts also for a further 24 h. Trimethoprim administration raised mean serum creatinine from 67 to 97 µmol/l, probably due to competitive inhibition of the tubular secretion of creatinine.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 45 (1993), S. 135-139 
    ISSN: 1432-1041
    Keywords: Furosemide ; protein binding ; pharmacokinetics ; renal function ; dehydration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have shown that, within therapeutic plasma concentrations, the unbound fraction of furosemide changes in direct proportion to the reciprocal of the plasma albumin concentration (correlation coefficient 0.99). Changes in the albumin concentration were produced by ultrafiltration of human plasma using a haemofiltration filter. Thus, we propose that, when studying changes in the pharmacokinetics of a highly protein bound drug, calculated changes in the unbound fraction offer an alternative to actual measurement of the unbound concentration, which is often difficult. Nine healthy volunteers receiving a continuous furosemide infusion were studied in normovolaemia and after dehydration (−1.4 kg), with and without pretreatment with an angiotensin converting enzyme inhibitor (captopril) or an a1-adrenoceptor blocking agent (prazosin). Significantly larger changes in the renal clearance of furosemide were found that could be explained by changes in the unbound fraction. Following dehydration, the unbound fraction of furosemide was decreased by about 5%, while its renal clearance fell by 27%, 33% and 13% after pretreatment with placebo, captopril and prazosin, respectively. The secretory clearance of the unbound furosemide changed substantially and in parallel with changes in the renal blood flow. It is suggested that changes in the renal clearance and excretion of furosemide and its t1/2 are much more dependent on changes in renal blood flow than on changes in its unbound fraction.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 0011-2240
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Chromatography B: Biomedical Sciences and Applications 225 (1981), S. 73-81 
    ISSN: 0378-4347
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 8
    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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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Journal of clinical monitoring and computing 11 (1994), S. 99-103 
    ISSN: 1573-2614
    Keywords: oxygen tension ; conjunctival ; blood volume ; cerebral blood flow ; sympathetic nervous activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Computer Science , Medicine
    Notes: Abstract An investigation of the feasibility and validity of measurement of the conjunctival oxygen tension as a monitor of peripheral circulation, blood and extracellular fluid volume and cerebral circulation was carried out in 7 healthy volunteers and 5 unconscious critical care patients with proven total cerebral infarction. The healthy volunteers were subjected to changes in hydration achieved by the administration of furosemide and subsequent rehydration by administration of normal saline. Conjunctival oxygen tension was found to be a sensitive indicator of changes in the degree of hydration presumably by its ability to detect changes in peripheral circulation depending upon circulating blood and extracellular fluid volume. A drawback is that other stimuli of the sympatho-adrenergic system such as temperature and pain, interfere with measurement in the conscious volunteer. In patients with presumed total brain infarction the conjunctival PO2 cannot be used as a reliable monitor of cerebral blood flow because of varying perfusion of the palpebral conjunctiva from the external carotid artery in the occasional patient.
    Type of Medium: Electronic Resource
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