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  • clearancebeta relationship  (1)
  • compounded peripheral bioavailability  (1)
  • deconvolution computer program  (1)
  • 1
    ISSN: 1573-8744
    Keywords: disposition decomposition analysis ; peripheral bioavailability ; compounded peripheral bioavailability ; AUC peripheral bioavailability ; distribution time ; maximum peripheral bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract Disposition decomposition analysis (DDA) is applied to evaluate the rate and extent of drug delivery from the sampling compartment to the peripheral system, i.e., peripheral bioavailability. Four parameters are introduced which are useful in quantifying peripheral bioavailability. The compounded peripheral bioavailability, Fcomp,is the ratio between the total compounded amount of drug transferred to the peripheral system and the injected dose, D.The AUCperipheral bioavailability, FAUC,is the ratio between the area under the amount vs.time curves for the peripheral system and the sampling compartment. The distribution time td,is the time following an i.v. bolus at which the net transfer of drug to the peripheral system reverses in direction. The maximum peripheral bioavailability, Fmax,is the maximum fraction of an i.v. bolus dose that is present in the peripheral system at any one time. Equations are derived which permit estimation of those parameters from drug concentrations in the sampling compartment. Simple algorithms and a computer program are provided for estimating Fcomp, FAUC, td, Fmax,and other parameters relevant to DDA for drugs that exhibit a linear polyexponential bolus response. Estimates of Ecomp, FAUC, td,are presented for several drugs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-8744
    Keywords: drug clearance ; log-linear slope ; beta correction ; clearance change ; clearancebeta relationship ; drug disposition decomposition ; clearance calculations ; drug elimination
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract An exact formula relating the terminal log-linear beta parameter and the drug clearance is derived. The expression is valid for drugs with a linear, polyexponential disposition kinetics. The formula is useful for calculating the clearance when the clearance has changed between drug administrations and requires only drug level data from the terminal, log-linear elimination phase in addition to data from a single separate i.v. administration in the same subject. Data from an i. v. administration are necessary in order to apply the disposition decomposition technique to isolate and uniquely define the distribution kinetics in terms of the distribution function h(t).The different clearances can then be calculated from the beta values of the log-linear terminal drug level data and the parameters of h(t).The theoretical basis of the method and its assumptions and limitations are discussed and various pertinent theorems are presented. A computer program enabling an easy implementation of the proposed method is also presented. The mathematical and computational procedures of the method are demonstrated using kinetic data from i.v. and oral administrations of cimetidine, diazepam, and pentobarbital in human subjects. The classical V. beta method of approximating the clearance as the product of volume of distribution and beta is considered for comparison. For the three drugs considered the V. beta method which assumes a single exponential disposition kinetics leads to excessive errors when applied in absolute clearance comparisons. However, when applied in relative comparisons in the form of the “beta correction” the errors cancel out to some extent depending on the magnitude of the distribution kinetic effect. Whenever possible it is advisable to apply the proposed method to avoid such errors.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1573-8744
    Keywords: deconvolution ; deconvolution algorithm ; deconvolution computer program ; ibuprofen dosage forms ; ibuprofenin vivo release ; meanin vivo dissolution timeMDT ; gastrointestinal bioavailability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract A new deconvolution algorithm (DCON) suitable for pharmacokinetic applications is presented. It requires that both the impulse and input responses, typically systemic drug levels, be well described by polyexponential equations. DCON has a wider range of applications than an earlier method (DECONV) from which it is derived. A FORTRAN program is provided, making implementation of the technique a simple matter. DCON is demonstrated to evaluate the “GI bioavailability,” defined as the rate and the extent of gastrointestinal drug release, of various ibuprofen dosage forms. The GI drug release kinetics exemplifies a pharmacokinetic system which cannot be evaluated using the previous deconvolution algorithm (DECONV) because of an initial zero drug level response. This limitation is not found in DCON. It is also demonstrated how the mean in vivo dissolution time MDT can be evaluated by deconvolution.
    Type of Medium: Electronic Resource
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