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An integrated approach to the pharmacokinetic analysis of drug absorption

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An Erratum to this article was published on 01 August 1975

Abstract

A systematic approach to the estimation of bioavailability using both model-independent and pharmacokinetic techniques is introduced. The methods of Kwan-Till and Wagner-Nelson or Loo-Riegelman are integrated such that one is able to check many of the assumptions inherent in these techniques and make appropriate adjustments for apparent deviations. The proposed integrated method makes use of all available data (both plasma and urine) and leads to a better understanding of the absorption, distribution, metabolism, and excretion of the drug being studied.

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Abbreviations

A(t) :

Cumulative amount of drug absorbed at timet

C p(t) :

Plasma concentration at timet

C T(t) :

Amount of drug in the tissue compartment divided by the volume of the central compartment

D :

Dose of drug administered

F :

Fraction of dose absorbed unmetabolized

f :

Fraction ofF · D excreted unchanged in the urine

U (t) :

Cumulative amount of drug excreted in the urine at timet

X T :

Amount of drug in the tissue compartment

δ :

Observed terminal slope for a one-compartment open model following nonintravascular drug administration

ɛ :

Observed slope on the residuals (estimate of the fast rate constant)

β :

Observed slow disposition rate constant for a two-compartment open model

k a :

First-order absorption rate constant

k e :

Elimination rate constant, one-compartment open model

k 13 :

Elimination rate constant, two-compartment open model

12, k21 :

Distribution rate constants, two-compartment open model

V d :

Apparent volume of distribution, one-compartment open model

V 1 :

Apparent volume of distribution of the central compartment for a two-compartment open model

Vcl,r :

Renal clearance of drug

Vcl,p :

Plasma clearance of drug

iv:

Drug administered intravenously

niv:

Drug administered by a nonvascular route

′:

Corrected on the basis of renal component of elimination alone

″:

Corrected on the basis of proportional changes in renal and nonrenal components of elimination

*:

Calculated by equation 22

W-N:

Wagner-Nelson

L-R:

Loo-Riegelman

K-T:

Kwan-Till

References

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Author information

Author notes

  1. Alice E. Till

    Present address: Department of Pharmacy, School of Pharmacy, University of California, 94143, San Francisco, California

Authors and Affiliations

  1. Merck Sharp and Dohme Research Laboratories, 19486, West Point, Pennsylvania

    Alice E. Till & K. C. Kwan

  2. Department of Pharmacy, School of Pharmacy, University of California, 94143, San Francisco, California

    Leslie Z. Benet

Authors
  1. Alice E. Till
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  2. Leslie Z. Benet
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  3. K. C. Kwan
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Additional information

An erratum to this article is available at http://dx.doi.org/10.1007/BF01066924.

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Till, A.E., Benet, L.Z. & Kwan, K.C. An integrated approach to the pharmacokinetic analysis of drug absorption. Journal of Pharmacokinetics and Biopharmaceutics 2, 525–544 (1974). https://doi.org/10.1007/BF01070946

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  • DOI: https://doi.org/10.1007/BF01070946

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