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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 46 (1994), S. 575-575 
    ISSN: 1432-1041
    Keywords: Renal clearance ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    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
    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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  • 5
    ISSN: 1573-7241
    Keywords: felodipine ; hypertension ; impaired renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Twenty-three patients with severe hypertension and impaired renal function were included in an open study of the efficacy and tolerance of felodipine treatment over 6 months. All patients were previously treated with a diuretic, a beta blocker, and a vasodilator, and eight of them also received an ACE inhibitor. At the start of felodipine treatment the previously used vasodilator was withdawn. In nine patients the concomitant antihypertensive treatment was reduced during the study. The glomerular filtration rate (GFR), as51Cr EDTA clearance, was determined before and at the end of the study. The blood pressure (BP) and heart rate (HR) were recorded at all clinical visits in the moring 12 hours after the evening dose of felodipine and 2 hours after the morning dose. Plasma concentrations of felodipine were measured at every visit before the morning dose and 2 hours after dose. The BP was reduced after felodipine was substituted for the previously used vasodilator. A significant additional antihypertensive effect was recorded 2 hours after the dose and amounted to −37±22/−15±12 mmHg (p=0.0001/p=0.0002) at 6 months. The effect measured 12 hours after the dose was less pronounced and was −11±28/−6±10 mmHg (p=0.15/p=0.03). Mean GFR was unchanged during the study, 38±19 versus 38±19 ml/min (n=16). There was a sixfold interindividual variation in the trough plasma concentrations at steady state at the same drug dosage. Higher plasma concentrations seemed to be required to achieve the same antihypertensive effects as in patients with less severe hypertension and normal renal function. The frequency of adverse effects and the number of patients withdrawn (n=5) were somewhat higher than reported in patients with normal renal function and may be related to the high doses (up to 80 mg daily) used. In conclusion our data suggest that felodipine, in addition to other antihypertensives, is effective and is usually well tolerated in the treatment of patients with severe hypertension and reduced renal function. In order to ensure a more even reduction of BP over the day, a tid dosage regimen of the plain-tablet formulation used in this study may be preferable.
    Type of Medium: Electronic Resource
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