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The Wagner‐Nelson method applied to a multicompartment model with zero order input
Author(s) -
Wagner John O.
Publication year - 1983
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510040408
Subject(s) - mathematics , theophylline , constant (computer programming) , coefficient of variation , bolus (digestion) , reaction rate constant , zero order , elimination rate constant , statistics , mathematical analysis , first order , surgery , pharmacokinetics , medicine , physics , kinetics , volume of distribution , quantum mechanics , computer science , programming language
It is shown that the Wagner‐Nelson absorption method provides zero‐order input rate constants exactly, or with small error, in a large number of cases where the two‐compartment open disposition model applies. Factors affecting the accuracy of the method were studied with error‐free simulated data. The method was applied to real data for three drugs. With ethanol infused over 2 h in eight human trials the estimated rate constant averaged 99·6 per cent of the known rate constant with a coefficient of variation of 6·86 per cent. With pindolol infused over 3 h in five human subjects the estimated rate constant averaged 98·7 per cent of the known rate constant with a coefficient of variation of 22·5 per cent. With theophylline administered orally in a sustained‐release form to seven human subjects the Wagner‐Nelson method provided estimated zero‐order rate constants which averaged 95·8 per cent of those estimated by an exact two‐compartment absorption equation with a coefficient of variation of 38·1 per cent (in this case bolus intravenous data were available for the same subjects).