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  • Articles: DFG German National Licenses  (3)
  • first-pass metabolism  (2)
  • Children  (1)
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  • Articles: DFG German National Licenses  (3)
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  • 1
    Electronic Resource
    Electronic Resource
    Cimetidine pharmacokinetics and dosage requirements in children (1985)
    Springer
    European journal of pediatrics 144 (1985), S. 72-76 
    Details
    ISSN: 1432-1076
    Keywords: Cimetidine ; Children ; Pharmacokinetics ; Halflife ; Clearance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics of cimetidine (10 mg/kg) were investigated in 11 children following an oral dose and in 9 children following an intravenous dose. The children ranged in age from 4–13 years and were undergoing radiology for upper gastrointestinal tract pain. Compared with a group of adults, the children had a higher total body clearance (11.6±3.4 versus 7.0±2.5 ml/min per kg; P〈0.005), a larger apparent volume of distribution (1.24±0.40 versus 0.80±0.24 l/kg; P〈0.005) and a shorter elimination half-life (83±26 versus 122±16 min; P〈0.001) of cimetidine. Renal clearance in children comprised 70% of total body clearance, more than double that of adults (9.0±1.9 versus 4.2±2.1 ml/min per kg; P〈0.001). The area under the cimetidine plasma concentration: time curve after the oral dose was on average 42% in children compared with adults. The mechanism for the increased elimination of cimetidine in children is suggested to be an increase in the renal tubular secretory transport of cimetidine in the kidney. A statistically significant negative correlatio was observed between age and cimetidine renal clearance. A cimetidine dosage regimen of approximately 30 mg/kg per day in three to four divided doses would be an appropriate dose in children.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00491931
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    Paper (German National Licenses)
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  • 2
    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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    Paper (German National Licenses)
    Fulltext
  • 3
    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
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
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