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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 48 (1995), S. 385-390 
    ISSN: 1432-1041
    Keywords: Furosemide ; Dialysis ; continuous ambulatory peritoneal ; drug disposition ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Single doses of oral and intravenous furosemide were given to 8 healthy male volunteers (40 mg) and 11 patients with renal failure maintained on continuous ambulatory peritoneal dialysis (CAPD) (80 mg). In the volunteers, absorption was variable. Only one half of the intravenous dose and one third of the oral dose was available for renal pharmacological action as judged by the urinary recovery. In the patients, absorption was also variable and was markedly delayed (t max 128 vs 90 min) but more complete (bioavailability 70.1 vs 53.6%). The differences between the two groups were not significant, however (95% C.I.: -90 to 30 and -40.4 to 7.5 respectively). The mean elimination half-life was significantly longer in the patients following both the oral (228 vs 65.1 min) and intravenous dose (195 vs 60.3 min). The total body clearance of furosemide in the volunteers was 138 ml·min−1 and this was much lower in the CAPD patients (61.9 ml·min−1) in whom the renal clearance was minimal. The peritoneal clearance of furosemide was negligible. Although there were trends indicating differences in absorption between the two groups, the significant differences in furosemide disposition observed in CAPD patients were due to renal failure.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical pharmacology 36 (1989), S. 291-297 
    ISSN: 1432-1041
    Keywords: paracetamol ; renal failure ; drug disposition ; polar metabolites ; cumulation ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of paracetamol following an oral dose of 1.0 g was compared in 10 healthy volunteers, 7 patients with moderate chronic renal failure and 6 patients with end stage renal failure on maintenance haemodialysis. Paracetamol absorption was normal in the patients with renal failure. The mean plasma half-life of paracetamol from 2 to 8 h was similar in the 3 groups (2.1 to 2.3 h) but from 8 to 24 h it disappeared much more slowly in the renal failure patients (half-life 11.7 compared with 4.9 h in the healthy volunteers). Plasma concentrations of paracetamol glucuronide and sulphate conjugates were greatly increased in the patients with moderate renal failure and the mean plasma half-lives were 30.5 and 21.8 h respectively compared with about 3 h in the healthy volunteers. Plasma concentrations of these metabolites were even higher in the dialysis patients and there was no significant fall over 24 h. The cysteine and mercapturic acid conjugates of paracetamol could only be measured in plasma in the patients with renal failure and concentrations were very low. The fractional urinary recovery of paracetamol and its glucuronide, sulphate, cysteine and mercapturic acid conjugates was similar in healthy volunteers and patients with moderate renal failure. The mean renal clearances of paracetamol and its glucuronide and sulphate conjugates in the healthy volunteers and patients with moderate renal failure were 15.7, 137 and 172, and 5.9, 14.5 and 14.8 ml/min respectively. In the latter patients the mean renal clearances of the cysteine and mercapturic acid conjugates were much greater at 35.4 and 80.2 ml/min. In the patients with moderate renal failure the AUC's of the glucuronide and sulphate conjugates were related to the plasma creatinine and there were significant negative correlations with the renal clearances of these metabolites and total urinary recovery. Marked cumulation of the polar glucuronide and sulphate conjugates of paracetamol would seem inevitable in patients with renal failure and the parent drug is apparently regenerated to a limited extent from retained metabolites.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1041
    Keywords: Paracetamol ; Renal failure ; glucuronide conjugation ; sulphate conjugation ; multiple dosing ; accumulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary We have compared the disposition of oral paracetamol (1.0 g t.d.s. for 10 days) in 6 healthy volunteers and 6 conservatively-managed patients with chronic renal failure (mean plasma creatinine 451 μmol·l−1). Blood was sampled daily for 10 days before the morning dose of paracetamol. Each day the pretreatment plasma concentrations of paracetamol were higher in the renal failure patients than in the volunteers, with mean values over the 10 days of 3.1 and 1.1 mg·l−1 respectively. The mean daily plasma concentrations of the sulphate and glucuronide conjugates of paracetamol were markedly higher in the renal failure group and apparent steady-state concentrations of about 25 and 85 mg·1−1 were reached on the 2nd and 6th days respectively. The mean steady-state plasma concentrations of the glucuronide conjugate on the 7th to 10th days of treatment were positively correlated with the plasma creatinine concentration (r=0.97), but this relationship did not hold for the sulphate conjugate. Cysteine and mercapturate conjugates could only be detected in one patient. Predictions of steady-state concentrations based on previous studies with single doses of paracetamol in renal failure patients were remarkably accurate for the glucuronide but not for the sulphate conjugate. These results are consistent with some extra-renal elimination of retained paracetamol conjugates in patients with chronic renal failure, with limited regeneration of the parent compound. The sulphate metabolite did not accumulate as predicted, possibly because of depletion of inorganic sulphate.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1041
    Keywords: Paracetamol ; Renal failure ; haemodialysis ; sulphate conjugation ; glucuronide conjugation ; accumulation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The disposition of oral paracetamol (1.0 g 3 times daily for 10 days) was studied in 6 patients with end-stage renal failure (creatinine clearance 〈5 ml×min−1) maintained on haemodialysis 2 or 3 times per week. Blood was sampled daily for 10 days. The time of sampling depended on whether the patients were dialysed in the morning or afternoon but was always within 5 h of the last dose of paracetamol. On dialysis days samples were taken at the start of the session. The mean plasma concentration of paracetamol was 6.8mg× 1−1 after the first 24 h and subsequently varied little throughout the 10 days. Apparent steady-state plasma concentrations of 60.0 mg×1−1 and 54.5 mg×1−1 were reached for the glucuronide and sulphate conjugate of paracetamol respectively by the 2nd day of treatment with little variation throughout the remainder of the study. These steady-state concentrations of paracetamol glucuronide and sulphate were much lower than predicted. The steady-state plasma concentrations of the retained cysteine and mercapturate conjugates of paracetamol were low (5.7 and 3.7 mg×1−1, respectively) and there was no evidence of accumulation of these potentially toxic metabolites. It is not clear why regular dosing with paracetamol in haemodialysis patients did not cause the accumulation of paracetamol glucuronide or sulphate as predicted. There may be enterohepatic elimination of retained paracetamol conjugates or depletion of substrates such as inorganic sulphate during chronic dosing.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0827
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1619-1560
    Keywords: Chronic renal failure ; Autonomic nervous system ; Parasympathetic ; Heart rate ; Heart rate variability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Heart rate variability was measured from 24-h electrocardiograms in 61 patients with end stage chronic renal failure. The method used counts the number of times successive RR intervals differ by more than 50 ms over the 24-h period, and is a reliable indicator of cardiac parasympathetic activity. Also analysed were the frequency and type of ectopic beats and other arrhythmias. Twentyone subjects (34%) had varying numbers of ventricular ectopic beats, and twelve (20%) had frequent supraventricular ectopics. Total 24-h count values were abnormal in 30 (76%) of the 41 subjects whose tapes were technically suitable for this analysis. There were no sex differences, but those patients maintained on haemodialysis had significantly lower counts than those on continuous ambulatory peritoneal dialysis. We conclude that about three-quarters of patients with chronic renal failure have abnormal cardiac parasympathetic activity. This may increase susceptibility to cardiac arrhythmias and sudden death and contribute to the high mortality of patients with chronic renal failure.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Digestive diseases and sciences 21 (1976), S. 337-339 
    ISSN: 1573-2568
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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