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  • 1
    Electronic Resource
    Electronic Resource
    Effect of plasma protein binding on drug disposition in muscle tissue: Application of statistical moment analysis and network theory toin situ local single-pass perfusion system (1988)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 16 (1988), S. 129-149 
    Details
    ISSN: 1573-8744
    Keywords: local perfusion system ; statistical moment theory ; drug disposition ; rabbit muscle tissue ; mitomycin C ; lipophilic derivative ; plasma protein binding ; network theory ; single-pass system analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The local disposition characteristics of mitomycin C (MMC) and five lipophilic prodrugs in rabbit hind leg muscle were examined using an in situ single-pass perfusion experiment. Test compounds inputted into a perfusion line as a rectangular function (unit pulse) were perfused with or without albumin and their outflow patterns were analyzed by statistical moment analysis. In interpretation of statistical moment parameters, the well-stirred model was applied to the local perfusion system based on the plate theory of a chromatographic system and some general pharmacokinetic parameters (the disposition parameters) were derived from the moments. A new theory which elucidates the relationships among the moments for plasma protein binding, unbound (free), and total drug fraction was established based on network theory. Using this system, the following conclusions were made for mitomycin C and its five lipophilic derivatives: (i) In the absence of albumin, an increase in lipophilicity led to an increase in organ clearance and distribution volume; (ii) drug bound to albumin did not transfer to the extravascular space; (iii) in the presence of albumin, an increase in lipophilicity results in a decrease in clearance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062256
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    A new method for assessment of drug disposition in muscle: Application of statistical moment theory to local perfusion systems (1985)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 13 (1985), S. 609-631 
    Details
    ISSN: 1573-8744
    Keywords: local perfusion system ; statistical moment theory ; drug disposition ; rabbit muscle tissue ; mitomycin C ; lipophilic derivative ; tissue distribution ratio ; mean elimination time ; dispersion ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new experimental system is used to determine exact information concerning local drug disposition. Rabbit hind leg is perfused in situusing a single-pass technique, and outflow curves of drugs are analyzed using statistical moment theory. By the introduction of Chromatographic concepts and the application of the well-stirred model to the local perfusion system, physiologically and/or physicochemically meaningful parameters are derived from the first three moments. Moreover, in the assessment, drug disposition is divided into elimination and distribution. The elimination process is also evaluated with respect to rate and extent. This system is used to elucidate the disposition characteristics of mitomycin C and its lipophilic derivative nonyloxycarbonyl mitomycin C.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01058904
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Statistical Moment Analysis of Hepatobiliary Transport of Phenol Red in the Perfused Rat Liver (1989)
    Springer
    Pharmaceutical research 6 (1989), S. 140-146 
    Details
    ISSN: 1573-904X
    Keywords: phenol red ; rat liver perfusion ; hepatic uptake ; metabolism ; biliary excretion ; moment analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new experimental system was applied to study hepatobiliary transport of drugs. Rat livers were perfused using a single-pass technique, and phenol red was momentarily introduced to this system from the portal side. Outflow dilution patterns of phenol red were analyzed using statistical moment theory, and kinetic parameters of hepatic distribution and elimination of phenol red were calculated from moments, namely, the hepatic extraction ratio (E i) and elimination rate constant (k el,i). A larger distribution volume (V i) was obtained for phenol red than for 131I-human serum albumin (HSA) and 51Cr-red blood cells (RBC), indicating its extravascular diffusivity. The biliary excretion of conjugated phenol red was delayed relative to that of the free agent. The larger biliary mean transit time (t bile,conj.) represents the processes of biliary transport and intrahepatic metabolism. Further, the effects of dose and perfusion temperature on the hepatobiliary transport of phenol red were determined. With high doses or low perfusion temperatures (20 and 27°C), E i, k el,i, and intrinsic clearance (CLint,i) of phenol red and biliary recovery of free and conjugated phenol red (F bile,free, F bile,conj) significantly decreased. The temperature-dependent and saturable processes in hepatic uptake, metabolism, and biliary excretion of phenol red were assessable to moment analysis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015980525940
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Effect of Chronic Administration of Phenobarbital on the Hepatobiliary Transport of Phenol Red: Assessment by Statistical Moment Analysis (1992)
    Springer
    Pharmaceutical research 9 (1992), S. 908-914 
    Details
    ISSN: 1573-904X
    Keywords: hepatobiliary transport ; phenol red ; enzyme induction ; statistical moment analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The effect of enzyme induction on the hepatobiliary transport of phenol red (PR) in rats was investigated by application of a new analytical system to determine local drug disposition based on statistical moment theory (T. Kakutani et al., J. Pharmacokin. Bio-pharm. 13:609–631, 1985). Employing the moment parameters obtained from the time courses of plasma and biliary concentrations of PR and its metabolite after intravenous injection, the hepatobiliary transport of PR was theoretically assessed by separating it into component subprocesses such as hepatic uptake, hepatobiliary transfer, and intrahepatic metabolism. The results demonstrated that the acceleration of plasma disappearance of PR caused by pretreatment with phenobarbital (PB), known to induce hepatic enzyme systems, could be attributed to elevation of both hepatic and extrahepatic clearances. While PB did cause bile flow elevation (choleresis) and increased metabolism, these effects were shown to make little contribution to accelerated plasma disappearance of PR, since it was shown that the hepatobiliary excretion of PR was rate-limited by the intrahepatic transfer process, which was unaffected by PB treatment. From the results of this study, this experimental/analysis methodology seems to be useful in obtaining detailed information about hepatobiliary transport of the drug from in vivo data.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1015852916524
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    Paper (German National Licenses)
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