Library

X
feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 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
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Distribution Kinetics of Diazepam, Lidocaine and Antipyrine in the Isolated Perfused Rat Hindlimb (1997)
    Springer
    Pharmaceutical research 14 (1997), S. 1640-1643 
    Details
    ISSN: 1573-904X
    Keywords: pharmacokinetics ; indicator dilution ; permeability ; dispersion ; model
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1012198922671
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Does the Dose-Solubility Ratio Affect the Mean Dissolution Time of Drugs? (1999)
    Springer
    Pharmaceutical research 16 (1999), S. 1470-1476 
    Details
    ISSN: 1573-904X
    Keywords: dissolution ; model ; fractional dissolution rate ; mean dissolution time ; relative dispersion
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Purpose. To present a new model for describing drug dissolution. On the basis of the new model to characterize the dissolution profile by the distribution function of the random dissolution time of a drug molecule, which generalizes the classical first order model. Methods. Instead of assuming a constant fractional dissolution rate, as in the classical model, it is considered that the fractional dissolution rate is a decreasing function of the dissolved amount controlled by the dose-solubility ratio. The differential equation derived from this assumption is solved and the distribution measures (half-dissolution time, mean dissolution time, relative dispersion of the dissolution time, dissolution time density, and fractional dissolution rate) are calculated. Finally, instead of monotonically decreasing the fractional dissolution rate, a generalization resulting in zero dissolution rate at time origin is introduced. Results. The behavior of the model is divided into two regions defined by q, the ratio of the dose to the solubility level: q 〈 1 (complete dissolution of the dose, dissolution time) and q 〉 1 (saturation of the solution, saturation time). The singular case q = 1 is also treated and in this situation the mean as well as the relative dispersion of the dissolution time increase to infinity. The model was successfully fitted to data(l). Conclusions. This empirical model is descriptive without detailed physical reasoning behind its derivation. According to the model, the mean dissolution time is affected by the dose-solubility ratio. Although this prediction appears to be in accordance with preliminary application, further validation based on more suitable experimental data is required.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1018923714107
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...