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  • renal clearance  (3)
  • first-pass metabolism  (2)
  • 1
    Electronic Resource
    Electronic Resource
    Interaction of cimetidine with bisoprolol (1987)
    Springer
    European journal of clinical pharmacology 33 (1987), S. 109-110 
    Details
    ISSN: 1432-1041
    Keywords: bisoprolol ; cimetidine ; interaction ; renal clearance ; tubular secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00610393
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  • 2
    Electronic Resource
    Electronic Resource
    Cimetidine-procainamide pharmacokinetic interaction in man: Evidence of competition for tubular secretion of basic drugs (1983)
    Springer
    European journal of clinical pharmacology 25 (1983), S. 339-345 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; procainamide ; interaction ; renal clearance ; tubular secretion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The hypothesis that basic drugs can compete for active tubular secretion by the kidney was tested in six healthy volunteers by comparing the single dose pharmacokinetics of oral procainamide before and during a daily dose of cimetidine. The area under the procainamide plasma concentration-time curve was increased by cimetidine by an average of 35% from 27.0±0.3 µg/ml·h to 36.5±3.4 µg/ml·h. The elimination half-life increased from an harmonic mean of 2.92 to 3.68 h. The renal clearance of procainamide was reduced by cimetidine from 347±46 ml/min to 196±11 ml/min. All these results were statistically significant (p〈0.016). The area under the plasma concentration-time curve for n-acetylprocainamide was increased by a mean of 25% by cimetidine due to a significant (p〈0.016) reduction in renal clearance from 258±60 ml/min to 197±59 ml/min. The data suggests that cimetidine inhibits the tubular secretion of both procainamide and n-acetylprocainamide, and, if so, represents the first documented evidence for this type of drug interaction in man. The clinical implications from this study necessitate dosage adjustments of procainamide in patients being concomitantly treated with cimetidine. The interaction is pertinent not only for basic drugs that are cleared by the kidney, but also for metabolites of basic drugs and endogenous substances which require active transport into the lumen of the proximal tubule of the kidney for their elimination.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01037945
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  • 3
    Electronic Resource
    Electronic Resource
    Superiority of stable isotope techniques in the assessment of the bioavailability of drugs undergoing extensive first pass elimination (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 127-131 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; tablets ; relative bioavailability ; intraindividual changes ; first-pass metabolism ; stable isotope technique
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary Although the absorption of verapamil is almost complete after oral administration, its bioavailability is low due to extensive hepatic first-pass metabolism. Besides large interindividual differences in first-pass metabolism, pronounced day-to-day intraindividual variations in first-pass metabolism are observed, leading to erroneous results in relative bioavailability studies. Stable isotope techniques, which permit simultaneous administration of a solution and a tablet, can successfully be used to overcome these difficulties. The method has the advantage that two experiments can be carried out in a single test. Furthermore, the number of subjects required in bioavailability studies can be greatly reduced. Using this technique the bioavailability of verapamil tablets (Isoptin® 80) relative to a stable labelled solution of verapamil was found to be 108.1%, with a 95% confidence interval between 89.1 and 127.1%.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00568399
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  • 4
    Electronic Resource
    Electronic Resource
    Influence of phenobarbital treatment on cimetidine kinetics (1981)
    Springer
    European journal of clinical pharmacology 19 (1981), S. 343-347 
    Details
    ISSN: 1432-1041
    Keywords: cimetidine ; phenobarbital ; gastro-intestinal absorption ; bioavailability ; renal clearance ; non-renal clearance ; enzyme induction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of orally administered cimetidine was studied in 8 healthy subjects before and after 3 weeks of treatment with phenobarbital 100 mg daily, and in a separate study 4 subjects received cimetidine intravenously before and after the administration of phenobarbital. There was no change in the volume of distribution, but total plasma clearance was increased by a mean of 18%, mainly due to a 37% increase in nonrenal clearance. Renal clearance and half-life were not significantly altered. The area under the plasma concentration-time curve after oral administration was significantly (P≪0.05) reduced by a mean of 15% after phenobarbital treatment. The amount of cimetidine excreted in urine and its sulphoxide metabolite were significantly (P〈0.05) reduced, on average by 34% and 26%, respectively by phenobarbital treatment. The data indicate that an apparent 20% reduction in the absorption of cimetidine was due to induction of gastrointestinal metabolism of cimetidine, with some contribution also from hepatic metabolism. Reduced absorption per se could not be totally excluded. Although the magnitude of the change was small, the finding of an 11% decrease in the time to achieve an effective plasma level of cimetidine after phenobarbital treatment may contribute to the ineffectiveness of cimetidine in certain patients.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00544584
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  • 5
    Electronic Resource
    Electronic Resource
    Inter- and intra-subject variation in the first-pass elimination of highly cleared drugs during chronic dosing (1984)
    Springer
    European journal of clinical pharmacology 26 (1984), S. 47-53 
    Details
    ISSN: 1432-1041
    Keywords: verapamil ; first-pass metabolism ; pharmacokinetics ; interindividual variation ; intraindividual variation ; chronic administration ; deuterated verapamil
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The pharmacokinetics of verapamil in five healthy volunteers were investigated on 4 occasions during chronic administration of deuterated verapamil. There was no statistically significant difference in oral clearance, terminal half-life, bioavailability, morning trough level and peak concentration or in the time of their occurrence on the four occasions. The plasma clearance, however, exhibited considerable inter- and intra-individual variation, ranging between 26.3% and 85.4% and 12.0% and 48.0%, respectively. Comparison of these pharmacokinetic parameters with data from previous single dose studies in the same subjects revealed a significant (p〈0.05) decrease in the clearance and an increase in the apparent bioavailability of verapamil during chronic administration, although no difference in the half-life was found. Due to the considerable variation in the oral clearance of verapamil during chronic dosing, steady-state conditions in a strict pharmacokinetic sense may never be attained, and pharmacokinetic data obtained in single dose studies will be of limited value in predicting steady-state plasma concentrations.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00546708
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