ISSN:
1573-8744
Keywords:
acetaminophen
;
oral administration
;
plasma levels
;
simultaneous fitting
;
weighting factor
;
central compartment correction factor
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Average and individual sets of plasma concentration-time data for acetaminophen following two oral treatments were simultaneously fitted to the integrated equation describing the two-compartment open model with first-order absorption and lag time. The nonlinear least-squares program NONLIN and an IBM 360/67 digital computer were employed to estimate nine parameters (kA, kB, C A 0 , C B 0 , k12, k21, kel, $$t_{0_A } $$ and $$t_{0_B } $$ ).When the mean plasma concentrations were weighted according to the inverse of their variances, the parameter estimates more accurately reflected those for individual subjects in the disposition portion of the model. Depending on the relative magnitudes of the disposition rate constants (k12, k21,and kel),the one-compartment open model can be used to predict equilibrium-state plasma levels even though the drug is really “two compartment.” Equations are presented which show when the one-compartment approximation is justified. Equations are also presented for calculation of loading doses for multiple dose regimens of any drug obeying the two-compartment open model and the equations are applied to acetaminophen.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01071309
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