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  • 1
    Electronic Resource
    Electronic Resource
    Multiple dose kinetics of ofloxacin and ofloxacin metabolites in haemodialysis patients (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 95-99 
    Details
    ISSN: 1432-1041
    Keywords: Ofloxacin ; Haemodialysis ; ofloxacin metabolites ; pharmacokinetics ; multiple doses ; dosage selection ; renal failure ; adverse effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary 7 patients with end-stage renal disease on regular haemodialysis were treated orally with a loading dose of 200 mg ofloxacin and multiple maintenance doses of 100 mg per 24 h for 10 days. The pharmacokinetics of ofloxacin and its metabolites were studied at the end of the treatment period. Plasma and dialysate concentrations of ofloxacin and ofloxacin metabolites were measured by HPLC. Peak (3.1 mg·1−1) and trough levels (1.6 mg·1−1) and the AUC of ofloxacin were comparable to the values in healthy volunteers given 300 to 400 mg ofloxacin p.o. The mean half-life, determined in the dialysis-free interval (t1/2β) and during the haemodialysis session (t1/2HD), was 38.5 h and 9.9 h, respectively. Extrarenal clearance (32.7 ml·min−1) was unchanged as compared to that reported in healthy volunteers after a single dose of ofloxacin. The fractional removal by haemodialysis amounted to 21.5%. Two metabolites, ofloxacin-N-oxide and demethyl-ofloxacin, were detected in plasma. Despite prolonged t1/2β of both metabolites (66.1 and 50.9 h) and multiple doses of ofloxacin the peak concentrations of the metabolites reached only 14% and 5% of that of the parent drug, respectively. It is concluded that in patients on regular haemodialysis treatment the dosage adjustment employed resulted in safe and therapeutically favourable plasma concentrations. The observed accumulation of ofloxacin metabolites does not appear to have any toxic or therapeutic significance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314927
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  • 2
    Electronic Resource
    Electronic Resource
    Antipyrine metabolite formation and excretion in patients with chronic renal failure (1985)
    Springer
    European journal of clinical pharmacology 28 (1985), S. 589-595 
    Details
    ISSN: 1432-1041
    Keywords: antipyrine ; chronic renal failure ; drug metabolism ; metabolism ; cumulation ; renal excretion ; pharmacokinetics ; clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary In the present study the influence of chronic renal insufficiency on antipyrine clearance, metabolite formation and excretion was investigated in 8 patients. After oral administration of antipyrine, the parent compound, its metabolites and their conjugates were assayed in plasma and urine. Besides the parent drug, 3-hydroxymethylantipyrine (HMA) was present in plasma in the free and conjugated forms, whereas 4-hydroxyantipyrine (OHA) and norantipyrine (NORA) were found only in the conjugated form. The same was true for urine. The plasma concentrations of these metabolites are too low to be measured in subjects with normal renal function. Plasma antipyrine clearance in the patients was in the same range as in healthy subjects. Investigation of metabolite kinetics, however, revealed that the rate of formation of NORA was preferentially decreased, whereas that of OHA and HMA were unaltered. Renal clearance of the metabolites of antipyrine was severely impaired in patients with renal insufficiency, and the resulting accumulation made it possible for the first-time to measure the antipyrine metabolites in plasma. Mean residence times of metabolites were longer than that of the parent compound. Renal clearances of the conjugates were correlated with the creatinine clearance, but were somewhat higher. Renal clearance of free HMA was lower and was also correlated with creatinine clearance. The mean clearance for glucuronidation of HMA was 93.1 ml/min. The results suggest that in healthy subjects Phase I metabolism is the rate-limiting step in the elimination of antipyrine, which is essential for its application as a model drug in metabolism studies.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544072
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  • 3
    Electronic Resource
    Electronic Resource
    Urinary excretion ofD-glucaric acid, an indicator of drug metabolizing enzyme activity, in patients with impaired renal function (1980)
    Springer
    European journal of clinical pharmacology 18 (1980), S. 255-261 
    Details
    ISSN: 1432-1041
    Keywords: D-glucaric acid ; renal insufficiency ; phenobarbital ; dipyrone ; cortisol ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The urinary excretion rate ofD-glucaric acid, an in vivo parameter of the activity of drug metabolizing enzymes, has been determined in patients with chronic renal insufficiency (glomerular filtration rate 4.5–80 ml/min/1.73 m2). The mean value of 22.3 µmoles/d (SD 7.2; n 28) was almost identical to that of healthy controls (22.1 µmoles/d, SD 7.3; n 22). Thus, no inhibitory or enhancing effect of renal insufficiency could be detected. The ability of this parameter to indicate alterations in the activity of hepatic drug metabolism, even in patients with renal insufficiency, was demonstrated by the increased excretion rate of glucaric acid (107 µmoles/d, SD 43.5; n 8; p〈0.001) after treatment for 7 days with the enzyme inducer phenobarbital. No significant correlation was found between glucaric acid excretion and sex, age, body weight or body surface in 50 patients. Glucaric acid excretion, therefore, should not be related to the creatinine content of urine samples, since creatinine excretion decreases with severity of renal insufficiency and varies with sex, age, body weight and many other conditions. A single dose of dipyrone (Novalgin®), a further in vivo indicator of drug metabolism, increased glucaric acid excretion on the same day, but no interference was found after a single dose of cortisol.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00563008
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics of mepindolol in patients with chronic renal failure (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 429-433 
    Details
    ISSN: 1432-1041
    Keywords: mepindolol ; renal failure ; haemodialysis ; pharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Five patients with a creatinine clearance of 14 to 37 ml/min/1.73 m2 were each given an oral dose of 10 mg of the beta-blocker mepindolol sulphate (Corindolan). In addition, two dialysis patients received the same dose either during hemodialysis or on a dialysis-free day. Plasma levels of mepindolol were measured by a sensitive, specific HPLC method. Mepindolol was rapidly absorbed in all the patients. The maximum plasma level of 35±8 ng/ml was reached after 1.4±0.5 h. The half-life of disposition was 4.0±1.5 h. The area under the plasma concentration-time curve was 237±84 ng × h/ml. The data obtained were no different from those found in normal healthy volunteers.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00549590
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  • 5
    Electronic Resource
    Electronic Resource
    Severe panarteritis associated with drug abuse (1999)
    Springer
    Intensive care medicine 25 (1999), S. 113-117 
    Details
    ISSN: 1432-1238
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of panarteritis with purpura fulminans, mononeuritis multiplex, gastrointestinal manifestation and presumably cardiac involvement in a previously healthy 22-year-old man with a history of drug abuse including cocaine, cannabinoids and methamphetamines is described. Histopathological examination of the gut led to the diagnosis of panarteritis without immune deposits. Antineutrophil antibodies were negative. Besides the drugs, no other possible cause of vasculitis was found. The patient recovered completely after 1 year. Drug abuse is a thus possible cause of severe extracerebral disabling vasculitis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001340050797
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