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  • activated charcoal  (1)
  • clearancebeta relationship  (1)
  • deconvolution computer program  (1)
  • 1
    ISSN: 1573-8744
    Keywords: linear systems analysis ; deconvolution ; induced drug removal ; activated charcoal ; phenobarbital ; hemodialysis ; peritoneal dialysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology
    Notes: Abstract The theory of linear systems analysis is applied to the evaluation of induced drug removal processes. The rate and extent of removal are determined by deconvolution for the case of phenobarbital removal from the systemic circulation by orally administered activated charcoal. The proposed method is model independent in the sense that no specific models of intrinsic or induced pharmacokinetic processes are required, and it is readily adapted to the analysis of most types of induced removal processes (hemodialysis, peritoneal dialysis, etc.). Application of the approach indicates that phenobarbital was removed from the systemic circulation to an extent of 25–53% following multiple oral doses of activated charcoal in healthy human subjects.
    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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