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  • 1
    Electronic Resource
    Electronic Resource
    Increased Sensitivity to the Anticonvulsant Effect of Valproate in Aging BN/BiRij Rats (1993)
    Springer
    Pharmaceutical research 10 (1993), S. 1046-1051 
    Details
    ISSN: 1573-904X
    Keywords: pharmacodynamics ; valproate ; aging ; anticonvulsive
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The aim of the present investigations was to study the influence of increasing age on the pharmacodynamics of valproate in BN/BiRij rats, applying a threshold for electrically induced localized seizure activity as a measure of the anticonvulsant effect. Seven groups of healthy male BN/BiRij rats were used, aged 3, 6, 12, 19, 25, 31, and 37 months. Individual plasma concentration versus anticonvulsant effect relationships were determined during a continuous intravenous infusion of sodium valproate at a rate of 5.5 mg/min/kg. The infusion was terminated when the anticonvulsant effect intensity had reached the maximum attainable level or at a total infusion time of three hours. A nonlinear relationship between valproate concentration and anticonvulsant effect intensity was observed with no maximal effect in the concentration range up to 1200 mg · L−1. With increasing age a parallel shift in the concentration versus anticonvulsant effect relationships toward lower concentrations occurred. Thus increasing age appears to be associated with an increased sensitivity to the anticonvulsant effect of valproate.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018975025417
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Age and the Pharmacokinetic-Pharmacodynamic Relationship of Phenobarbital in Rats: “Pseudo”-Longitudinal vs Cross-Sectional Study Design (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 1456-1459 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; pharmacodynamics ; aging ; phenobarbital ; cross-sectional ; “pseudo”-longitudinal
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract In a previous study, an apparent age-related increase in brain sensitivity to the anesthetic effect of phenobarbital was observed in BN/BiRij rats. However, since this study was conducted according to a cross-sectional design, the observed change could, in principle, also have been the result of a cohort effect. The purpose of the present investigation was to exclude the role of such a cohort effect by adopting a “pseudo”-longitudinal study design. In this design 45 animals out of one cohort were reserved, and one subgroup was investigated at five ages (7, 14, 21, 29, and 34 months). A decrease in the anesthetic threshold dose of phenobarbital was found during aging, which appeared to be due mainly to an increase in the brain sensitivity. It is concluded that the previously observed increase in brain sensitivity is indeed the result of the aging process rather than a cohort effect.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015815014166
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
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