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  • 1
    Electronic Resource
    Electronic Resource
    Intra- and Intersubject Variability: Mixed-Effects Statistical Analysis of Repeated Doses of an Angiotensin Converting Enzyme Inhibitor, CGS 16617 (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 328-331 
    Details
    ISSN: 1573-904X
    Keywords: random-effects statistical model ; bioavailability trials ; biological variation ; intersubject variability ; intrasubject variability ; CGS 16617
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The intrasubject and intersubject variabilities for CGS 16617, an angiotensin converting enzyme inhibitor, were evaluated in an open-label, repeat single-dose bioavailability trial. Eight healthy male volunteers each received a 20-mg oral dose of CGS 16617 as an aqueous solution on four separate occasions. Components of variance were evaluated for a mixed-effects statistical model in which subjects were regarded as a random factor. While intersubject variability was statistically significant (P 〈 0.05) for all pharmacokinetic variables measured, AUC, C max, t 1/2, and t max, its contribution to the total observed variability was relatively small for AUC, t 1/2 and t max. The proportion of variation due to intrasubject variability was 70, 19, 61, and 72% for AUC, C max, t 1/2, and t max, respectively. Ramifications of the large intrasubject source component of variability as related to bioavailability trials and biological variation are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015954609527
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  • 2
    Electronic Resource
    Electronic Resource
    Correlation of mitochondrial form and function in vivo: Microinjection of substrate and nucleotides (1982)
    Springer
    Cell & tissue research 227 (1982), S. 129-137 
    Details
    ISSN: 1432-0878
    Keywords: Mitochondria ; Ultrastructure ; Microinjection ; ATP ; ADP ; Amoeba proteus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Microinjection of adenine nucleotides and substrates into the cytoplasm of Amoeba proteus followed by EM examination has been used in an attempt to relate alterations in mitochondrial morphology with functional changes. Contracted mitochondria with dark matrix and wide cristae (Type I), and expanded mitochondria with light matrix and narrower cristae (Type II) coexist in normal active amoebae, but their numbers can be varied according to different cell activity states. Following injection of ATP, the mitochondria of the amoebae showed a time-dependent movement towards a predominately Type II form, whilst injections of ADP produced predominately the Type I form. Injection of succinate or deionised water, even in large amounts, had little effect on the numbers of Type I or Type II forms. The change induced by ATP was of long duration; that induced by ADP was influenced by both concentration injected and the cell's substrate levels. With 3 mM solutions of ADP the mitochondrial population was primarily of Type I organelles; higher ADP concentrations or the simultaneous injection of succinate, however, resulted in a switch with time to increased proportions of Type II mitochondria. The results extend the findings of previous in vivo and in vitro mitochondrial studies and are discussed in the light of these.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00206336
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    Paper (German National Licenses)
    Fulltext
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