J. Urquhart, PHARMACODYNAMICS OF VARIABLE PATIENT COMPLIANCE - IMPLICATIONS FOR PHARMACEUTICAL VALUE, Advanced drug delivery reviews, 33(3), 1998, pp. 207-219
Pharmaceutical value, a multidimensional factor that includes proven e
fficacy, is now crucial to market success. A key parameter of value is
reliability in use, determined by the several sources of variance in
drug response, e.g. the Harter-Peck model, based on linear pharmacomet
rics of theophylline, whose dose-response has an estimated 80% coeffic
ient of variation, due mainly to variable pharmacokinetics and non-com
pliance. The main forms of non-compliance are multiday intervals betwe
en doses, the impact of which is difficult to assess because too littl
e is known of the time-course of drug actions after dosing stops ('off
-responses'). Omeprazole, the best-selling drug, is an exception, and
its off-response data reveal markedly non-linear pharmacodynamics that
appear to filter most of the variance that a linear model passes, pro
jecting a big gain in reliability. The impact of variable compliance i
s attenuated by 'forgiveness', the post-dose duration of effective act
ion (4-5 days for omeprazole) minus its recommended dosing interval. (
C) 1998 Elsevier Science B.V. All rights reserved.