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  • 1
    Electronic Resource
    Electronic Resource
    Response to furosemide during dehydration with and without naproxen pretreatment of kidney donors and renal transplant recipients (1991)
    Springer
    European journal of clinical pharmacology 40 (1991), S. 209-214 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00315197
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  • 2
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and effects of frusemide in patients with the nephrotic syndrome (1989)
    Springer
    European journal of clinical pharmacology 37 (1989), S. 173-180 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00558227
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Changes in renal clearance of furosemide due to changes in renal blood flow and plasma albumin concentration (1993)
    Springer
    European journal of clinical pharmacology 45 (1993), S. 135-139 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00315494
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    Paper (German National Licenses)
    Fulltext
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