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  • 1
    Electronic Resource
    Electronic Resource
    Generalizations in linear pharmacokinetics using properties of certain classes of residence time distributions. I. Log-convex drug disposition curves (1986)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 14 (1986), S. 635-657 
    Details
    ISSN: 1573-8744
    Keywords: drug disposition curve ; log-convexity ; residence time distribution ; noncompartmental analysis ; time-varying volume of distribution ; terminal exponential phase ; reliability theory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Introducing the phenomenoiogical concept of a time-varying fractional rate of elimination kD(t)and applying the theory of lifetime distributions, implications of the log-convexity of drug disposition curves are examined and some important applications are described. Linear pharmacokinetic systems exhibiting a log-convex impulse response and satisfying the basic conditions underlying the noncompartmental approach have the following properties: (1) The time-varying volume of distribution V(t)increases, and consequently the fractional rate of elimination kD(t)=CL/V(t)decreases monotonically. (2) The concentration-time curve and the time course of total amount of drug in the body, respectively, have an exponential tail [where V(t)approaches the equilibrium value VZ].The relative dispersion of residence times (CV D 2 =VDRT/MDRT2)and the ratio Vss/VZ (V ss is the volume of distribution at steady state) act as measures of departure from pure monoexponential decay (one-compartment behaviour). The role of the latter parameters as shape parameters of the curve that characterize the distributional properties of drugs is discussed. Upper and lower bounds of the time course of drug amount in the body are derived using the parameters MDRTand CV D 2 or λz (terminal exponential coefficient), respectively. This approach is also employed to construct upper bounds on the fractional error in AUCdetermination by numerical integration that is due to curve truncation. The significance of the fractional elimination rate concept as a unifying approach in interspecies pharmacokinetic scaling is pointed out. Some applications of the results are demonstrated, using digoxin data from the literature.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01067968
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  • 2
    Electronic Resource
    Electronic Resource
    Dynamics of drug distribution. I. Role of the second and third curve moments (1992)
    Springer
    Journal of pharmacokinetics and pharmacodynamics 20 (1992), S. 253-278 
    Details
    ISSN: 1573-8744
    Keywords: dynamics of drug distribution ; curve moments ; residence time distribution ; circulation time distribution ; variance ; skewness ; drug disposition curve ; mixing curve ; non-compartmental analysis ; recirculation model ; noneliminating and eliminating system
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Conventionally, the dynamics of distribution in the body is evaluated by the so-called distribution half-life (e.g., t 1/2,α but then the mean time of the distribution process is underestimated due tothe influence of elimination. By contrast, information about the dynamics of distribution contained in drug disposition curves can be extracted by the second and third curve moments, parameters that are related to the variance (VDRT)and skewness (SDRT)of residence time distributions; whereas the equilibrium state characterized by the volume of distribution (Vss), isdetermined by the mean residence time (MDRT)or the first curve moment. The approach represents a general noncompartmental analysis that is independent of a detailed structural model or a particular disposition function. Two parameters are introduced to characterize the dynamics of drug distribution: (i)the degree of departure of the system from “well-mixed” behavior of instantaneous distribution equilibrium (related to VDRT)and (ii)the mean time until equilibration is achieved (mean equilibration time, MEQT),which additionally depends on SDRT.Both parameters are quantitative measures of the dynamics of distribution and display explicit physical significance in terms of distribution within the corresponding noneliminating system. It is further shown that the so-called “distribution phase” in biexponential disposition curves is related to a monoexponential mixing curve of its corresponding noneliminating system with an equilibration or mixing half-time, t 1/2,M =t 1/2,α (Vβ/V ss * ), where V ss * denotes the distribution volume of the noneliminating system. The results are applied to mixing and disposition curves measured for acetaminophen in liver-ligated and intact rats, respectively.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01062527
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  • 3
    Electronic Resource
    Electronic Resource
    RNA recognition by arginine-rich peptide motifs Amino acids and RNA bases are represented by standard three- or single-letter codes. (1998)
    New York : Wiley-Blackwell
    Biopolymers 48 (1998), S. 167-180 
    Details
    ISSN: 0006-3525
    Keywords: RNA recognition ; RNA binding proteins ; arginine-rich motif ; Chemistry ; Polymer and Materials Science
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: A ubiquitious class of RNA-binding proteins is distinguished by an arginine-rich motif. Such proteins function in transcription, translation, RNA trafficking, and packaging. Peptide models are derived from viral regulatory proteins, including the virulence factors Tat and Rev of mammalian immunodeficiency viruses. Structures of model peptide-RNA complexes exhibit diverse strategies of recognition based in each case on structural transitions. Induced RNA structures contain noncanonical elements such as purine-purine mismatches, base triples, and flipped bases. Such elements enlarge and extend the RNA major groove to create specific peptide-binding pockets and surfaces. The repertoire of bound peptide structures - β-hairpin, α-helix, and helix-bend-helix - reflects the diversity of induced RNA architectures. This repertoire, reminiscent of primordial exon-encoded peptides, may recapitulate early events in the transition between RNA and protein worlds. Peptide-directed changes in modern RNA structures can provide a mechanism of signaling in higher-order RNA-protein assemblies. © 1999 John Wiley & Sons, Inc. Biopoly 48: 167-180, 1998
    Additional Material: 5 Ill.
    Type of Medium: Electronic Resource
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