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  • 1
    Electronic Resource
    Electronic Resource
    Effect of probenecid on the formation and elimination kinetics of the sulphate and glucuronide conjugates of diflunisal (1995)
    Springer
    European journal of clinical pharmacology 47 (1995), S. 519-523 
    Details
    ISSN: 1432-1041
    Keywords: Diflunisal ; Probenecid ; steady state pharmacokinetics ; glucuronidation ; drug interaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract The effect of probenecid on the pharmacokinetics of diflunisal and its glucuronide and sulphate conjugates was studied in 8 healthy volunteers. Diflunisal 250 mg b. d. was administered p. o. for 15 days and its steady state pharmacokinetics was evaluated on Day 16 after the last dose (control phase). Probenecid 500 mg b. d. was co-administered throughout the entire study period in the treatment phase of the study. The steady state plasma concentration of diflunisal was significantly higher during the probenecid treatment phase as compared to the control phase (104.0 vs. 63.1 μg·ml−1). This was the result of a significant decrease in the plasma clearance of diflunisal from 5.8 (control) to 3.4 ml·min−1 (probenecid co-administration). The metabolite formation clearances of both glucuronides were significantly decreased by probenecid, -45 % and -54 % for the phenolic and acyl glucuronide, respectively. The metabolite formation clearance of the sulphate conjugate was not affected by probenecid co-administration. Steady state plasma concentrations of the sulphate and glucuronide conjugates of diflunisal were 2.5- to 3.1-fold higher during probenecid co-administration, due to a significant reduction in the renal clearance of the three diflunisal conjugates. Probenecid also reduced the plasma protein binding of diflunisal, but only to a minor extent; the unbound plasma fraction of diflunisal at steady state averaged between 5 and 30 % higher during probenecid co-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00193705
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  • 2
    Electronic Resource
    Electronic Resource
    Does fenbufen have a large distribution volume or is it subject to extensive presystemic elimination? (1983)
    Springer
    European journal of clinical pharmacology 24 (1983), S. 137-138 
    Details
    ISSN: 1432-1041
    Keywords: fenbufen ; volume of distribution ; disposition
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00613940
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  • 3
    Electronic Resource
    Electronic Resource
    Acetylator phenotype and serum levels of sulfapyridine in patients with inflammatory bowel disease (1981)
    Springer
    European journal of clinical pharmacology 21 (1981), S. 243-250 
    Details
    ISSN: 1432-1041
    Keywords: sulfasalazine ; sulfapyridine ; acetylsulfapyridine ; inflammatory bowel disease ; toxicity ; rapid acetylator ; slow acetylator ; acetylator phenotype
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Twenty-eight outpatients receiving sulfasalazine for inflammatory bowel disease were monitored. Assessment of acetylator phenotype according to the percentage of acetylated sulfapyridine in serum provided a clear distinction between rapid and slow acetylators. In comparison, the percentage of acetylated sulfapyridine in saliva or urine was a less precise index of phenotype. Determination of saliva concentrations of sulfapyridine and N4-acetylsulfapyridine did not provide a reliable estimate of serum levels. Slow acetylators had significantly higher serum concentrations of sulfapyridine (21.9±14.0 [SD] µg/ml) than rapid acetylators (8.8±4.3 µg/ml) and had a higher incidence of toxicity (not statistically significant,p〉0.05). Serum concentrations of sulfapyridine were significantly higher in patients with symptoms of toxicity (23.2±15.9 µg/ml) than those without (13.9±9.5 µg/ml) (p〈0.05). However, serum concentrations of total sulfapyridine (sulfapyridine plus N4-acetylsulfapyridine) were not significantly different in patients with (32.9±21.2 µg/ml) or without (22.8±12.0 µg/ml) toxicity (p〉0.05). For all patients serum concentrations of sulfapyridine (total sulfapyridine) ranged from 3.5 to 73.1 (5.7 to 95.1) µg/ml in patients with controlled disease and 6.3 to 38.0 (14.0 to 54.7) µg/ml in patients with active disease. A significant correlation between clinical status of disease and serum drug concentrations was only apparent for rapid acetylators (p〈0.05). The daily sulfasalazine dosage (mg/kg of body weight, log value) and serum drug concentrations (log values) were highly correlated (p〈0.05). For clinical evaluation of inflammatory bowel disease patients determination of serum sulfapyridine concentrations appears to be more important for monitoring toxicity than therapeutic efficacy of sulfasalazine. Assessment of acetylator status appears to be useful for predicting serum sulfapyridine levels in patients receiving sulfasalazine therapy.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00627927
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of age and sex on the plasma binding of acidic and basic drugs (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 91-97 
    Details
    ISSN: 1432-1041
    Keywords: plasma protein binding ; age ; sex ; alpha1-acid glycoprotein ; albumin ; acidic drugs ; basic drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Protein binding of chlorpromazine, propranolol, meperidine, desipramine, salicylic acid and phenytoin was determined in plasma of 64 healthy volunteers (35 males and 29 females). An attempt was made to identify factors affecting the plasma protein binding of these drugs. Whereas plasma albumin levels decreased as a function of age in both sexes, α1-acid glycoprotein levels increased with age, but the increase was more pronounced in males. The free plasma fraction of the acidic drugs (salicylic acid, phenytoin) and despiramine (a base) showed a significant (p〈0.005) negative correlation with plasma albumin levels. The free fractions of the other three basic drugs (chlorpromazine, propranolol, meperidine) in plasma showed a significant (p〈0.005) negative correlation with α1-acid glycoprotein plasma levels. Plasma protein binding of salicylic acid, phenytoin and desipramine decreased as a function of age. Plasma protein binding of chlorpromazine, propranolol and meperidine was virtually unaffected by age or was slightly increased (chlorpromazine). Only in the case of salicylic acid could a statistically significant difference be demonstrated between males and females in the free fraction-age relationship. Stepwise multiple linear regression analysis, including age and blood chemistry values such as hematocrit, bilirubin, cholesterol, triglycerides, creatinine, BUN, albumin and α1-acid glycoprotein as independent variables, identified age as the variable explaining most of the variability in plasma binding of salicylic acid, phenytoin and desipramine. For chlorpromazine, propranolol and meperidine α1-acid glycoprotein was the most important determinant of plasma protein binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00553161
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  • 5
    Electronic Resource
    Electronic Resource
    Effect of age and sex on the plasma binding of acidic and basic drugs (1984)
    Springer
    European journal of clinical pharmacology 27 (1984), S. 91-97 
    Details
    ISSN: 1432-1041
    Keywords: plasma protein binding ; age ; sex ; alpha1-acid glycoprotein ; albumin ; acidic drugs ; basic drugs
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Protein binding of chlorpromazine, propranolol, meperidine, desipramine, salicylic acid and phenytoin was determined in plasma of 64 healthy volunteers (35 males and 29 females). An attempt was made to identify factors affecting the plasma protein binding of these drugs. Whereas plasma albumin levels decreased as a function of age in both sexes, α1-acid glycoprotein levels increased with age, but the increase was more pronounced in males. The free plasma fraction of the acidic drugs (salicylic acid, phenytoin) and despiramine (a base) showed a significant (p〈0.005) negative correlation with plasma albumin levels. The free fractions of the other three basic drugs (chlorpromazine, propranolol, meperidine) in plasma showed a significant (p〈0.005) negative correlation with α1-acid glycoprotein plasma levels. Plasma protein binding of salicylic acid, phenytoin and desipramine decreased as a function of age. Plasma protein binding of chlorpromazine, propranolol and meperidine was virtually unaffected by age or was slightly increased (chlorpromazine). Only in the case of salicylic acid could a statistically significant difference be demonstrated between males and females in the free fraction-age relationship. Stepwise multiple linear regression analysis, including age and blood chemistry values such as hematocrit, bilirubin, cholesterol, triglycerides, creatinine, BUN, albumin and α1-acid glycoprotein as independent variables, identified age as the variable explaining most of the variability in plasma binding of salicylic acid, phenytoin and desipramine. For chlorpromazine, propranolol and meperidine α1-acid glycoprotein was the most important determinant of plasma protein binding.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02395213
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  • 6
    Electronic Resource
    Electronic Resource
    Single and multiple dose pharmacokinetics of enteric coated ketoprofen: Effect of cimetidine (1988)
    Springer
    European journal of clinical pharmacology 35 (1988), S. 521-527 
    Details
    ISSN: 1432-1041
    Keywords: ketoprofen ; cimetidine ; enteric coated formulation ; pharmacokinetics ; co-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The effect of cimetidine on the single and multiple dose pharmacokinetics of enteric coated ketoprofen was studied in 12 healthy volunteers. Each subject completed two 8-day study treatment periods: either ketoprofen alone (100 mg p.o. twice daily), or co-administered with cimetidine (600 mg twice daily). tlag, Cmax, tmax, t1/2, and k for ketoprofen were not significantly different between single and multiple dose administration. AUC of ketoprofen was slightly but significantly larger following multiple (21.2 µg·h·ml−1) as compared to single dose administration (19.0 µg·h· ml−1). As a result, plasma clearance of ketoprofen was slightly but significantly reduced following multiple dose administration (80.6 ml/min vs 89.3 ml/min). Cimetidine had no effect on the single or multiple dose pharmacokinetics of enteric coated ketoprofen. Total 12-h urinary recovery of ketoprofen (mostly in the form of ketoprofen glucuronide) was 83.5% of the dose following single dose administration and was significantly greater following multiple dose administration (93.1%). Again cimetidine co-administration had no effect on the single and multiple dose urinary recovery. The results of this study show that cimetidine is not affecting the oral pharmacokinetics of enteric coated ketoprofen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00558248
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  • 7
    Electronic Resource
    Electronic Resource
    Circadian rhythm of serum sulfate levels in man and acetaminophen pharmacokinetics (1990)
    Springer
    European journal of clinical pharmacology 39 (1990), S. 143-148 
    Details
    ISSN: 1432-1041
    Keywords: Acetaminophen ; Serum inorganic sulfate ; Circadian rhythm ; Chronopharmacokinetics
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The circadian variation of serum inorganic sulfate levels was studied in healthy volunteers. The effect of subchronic acetaminophen administration (650 mg q.i.d. for 4 days) on serum inorganic sulfate levels was investigated and the possible role of fluctuating serum inorganic sulfate levels on the pharmacokinetics of acetaminophen was evaluated. During a 24 h cycle, serum inorganic sulfate levels were lowest in the morning (11.00 h) and typically increased in the afternoon to reach a maximum in the early evening (19.00 h). Average 24 h serum concentrations were 360 μM and the difference between minimum and maximum levels was on average 25.8%. Subchronic administration of acetaminophen (650 mg q.i.d. for 4 days) significantly reduced serum inorganic sulfate levels to a 24 h average of 253 μM. The circadian rhythm, however, was not affected and the difference between minimum (12.00 h) and maximum (18.50 h) serum concentrations was 31.3%. Subchronic acetaminophen administration lead to a significant decrease in the renal excretion (−51%) and renal clearance (−33%) of inorganic sulfate. No significant differences were found in the disposition kinetics of acetaminophen and its glucuronide and sulfate conjugates during two consecutive dosing intervals (08.00–14.00 h, 14.00–20.00 h) on Day 4 of the acetaminophen regimen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00280048
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  • 8
    Electronic Resource
    Electronic Resource
    Both phenolic and acyl glucuronidation pathways of diflunisal are impaired in liver cirrhosis (1992)
    Springer
    European journal of clinical pharmacology 42 (1992), S. 471-474 
    Details
    ISSN: 1432-1041
    Keywords: Diflunisal ; Cirrhosis ; glucuronidation sulfation ; protein binding
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of diflunisal, a salicylate derivative that undergoes phenolic and acyl glucuronidation as well as sulphate conjugation, has been studied after a single oral dose (250 mg) in patients with cirrhosis (n=5) and in healthy controls (n=5). The plasma clearance of total (bound + unbound) diflunisal was 10.2 ml · min−1 in the control subjects and it was not affected by cirrhosis (10.9 ml · min−1). The plasma protein binding of diflunisal was significantly reduced in cirrhosis; the percentage of unbound diflunisal in plasma was 0.089 in the controls and 0.147 in the patients with cirrhosis. Plasma clearance of unbound diflunisal was significantly impaired in cirrhosis: 11.51 · min−1 in control subjects vs 7.41 · min−1 in cirrhotics. In cirrhotic patients, the unbound partial clearances to the phenolic and acyl glucuronides were both significantly reduced, by approximately 38%. The unbound partial clearance to the sulphate conjugate was not significantly affected by cirrhosis. The results show that both the phenolic and acyl glucuronidation pathways of diflunisal are equally susceptible to the effects of liver cirrhosis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00314852
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  • 9
    Electronic Resource
    Electronic Resource
    The effect of acetaminophen administration on its disposition and body stores of sulphate (1986)
    Springer
    European journal of clinical pharmacology 30 (1986), S. 273-278 
    Details
    ISSN: 1432-1041
    Keywords: acetaminophen ; chronic therapy ; disposition ; sulfate stores ; serum sulfate
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary This investigation was designed to investigate the effects of ingestion of multiple therapeutic doses of acetaminophen on the disposition of the drug and on the cosubstrate, sulfate. Nine healthy volunteers and nine outpatients receiving acetaminophen for chronic pain were involved in the study. Volunteers were given a single 650 mg oral dose of acetaminophen. One week later they were given 650 mg of acetaminophen every six hours for five doses. Patients were maintained on their normal treatment and dosage schedules (600 mg every 3 to 8 h) for the study. In healthy volunteers the half-life of acetaminophen after single and multiple dosing was not significantly different. However, the fraction of acetaminophen recovered in the urine as the sulfate conjugate was less and the glucuronde conjugate greater after multiple dosing than after a single of the drug. There was no difference in the percentage recovered as the-parent compound between single and multiple dosing. Serum sulfate levels fluctuated over the 6-h period following administration of single and multiple doses of acetaminophen to volunteers. The mean serum sulfate concentration was less after administration of five sequential 650 mg doses of acetaminophen than after a single dose. The renal clearance of inorganic sulfate showed a corresponding decrease. Unexpectedly, patients on chronic acetaminophen therapy exhibited elevated serum sulfate levels (levels higher than the maximum sulfate concentration seen in volunteers).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00541527
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  • 10
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    Acetylator phenotype and serum levels of sulfapyridine in patients with inflammatory bowel disease (1981)
    Springer
    Details
    Publication Date: 1981-01-01
    Print ISSN: 0031-6970
    Electronic ISSN: 1432-1041
    Topics: Chemistry and Pharmacology , Medicine
    Published by Springer
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