Pharmacokinetics as an Aid to Optimising Compliance with Medications

Abstract

Most ambulatory therapeutics employ long term administration of oral medications, both for relief of symptoms and for prophylaxis against long term complications of disease. In an ideal world, all diagnoses would be unambiguous, and all patients' adherence to the prescribed regimens would be at or near optimal. In such an idealised setting, clinicians' and investigators' knowledge of biological and pharmacological variance would be sufficient to assess and optimise the outcome of drug therapy.Reality, however, is quite different. Even in those highly selected populations participating in clinical trials, with frequent and close supervision, the medication-taking behaviour of individuals frequently exhibits profound and largely unpredictable variability)'] One major consequence of such variability is increased ambiguity for the clinician. This review will focus on the interpretive dilemma faced by clinicians in practice settings, despite the advent of sophisticated pharmacokinetic analysis and simplified, once-daily regimens.

A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self‐Administered Questionnaires

“…Here we found a nonadherence rate of 14.5% with HCQ levels only and 18.4% when we also considered undetectable DCQ levels. These percentages are in keeping with the 5–10% of patients who completely stopped or frequently interrupted tablet ingestion in studies using electronic monitoring . Blood drug level measurements can objectively detect only severe nonadherence (i.e., absence of any treatment or intake of only a few tablets), since high HCQ levels may be reached within days after treatment resumes due especially to flares or simply the “white‐coat” compliance effect .…”

“…The lack of overlap between questionnaires and drug levels, which probably measure different patterns of nonadherence, is reflected by the moderate correlation between these methods. Thus, two separate and independent patterns of nonadherence have been described: (i) tablets missed relatively infrequently (but more than 20%), and (ii) tablet intake completely stopped or frequently interrupted and erratic. Interestingly, some patients with undetectable levels of both HCQ and DCQ (i.e., who had not taken any treatment for some time) had MASRI scores greater than 80%.…”

“…These percentages are in keeping with the 5-10% of patients who completely stopped or frequently interrupted tablet ingestion in studies using electronic monitoring. 43,44 Blood drug level measurements can objectively detect only severe nonadherence (i.e., absence of any treatment or intake of only a few tablets), since high HCQ levels may be reached within days after treatment resumes 19 due especially to flares or simply the "white-coat" compliance effect. 2 Accordingly, rates of nonadherence by drug levels are likely to reveal only the tip of the iceberg.…”

Note of Republication: A Prospective International Study on Adherence to Treatment in 305 Patients With Flaring SLE: Assessment by Drug Levels and Self‐Administered Questionnaires

“…These percentages are in keeping with the 5–10% of patients who completely stopped or frequently interrupted tablet ingestion in studies using electronic monitoring. 43, 44 Blood drug level measurements can objectively detect only severe nonadherence (i.e. absence of any treatment or intake of only a few tablets), since high HCQ levels may be reached within days after treatment resumes 19 due especially to flares or simply the ‘white-coat’ compliance effect.…”

“…The lack of overlap between questionnaires and drug levels, which probably measure different patterns of nonadherence, is reflected by the moderate correlation between these methods. Thus, two separate and independent patterns of nonadherence have been described: 43 (a) tablets missed relatively infrequently (but more than 20%) and (b) tablet intake completely stopped or frequently interrupted and erratic. Interestingly, some patients with undetectable levels of both HCQ and DCQ (i.e., who had not taken any treatment for some time) had MASRI scores greater than 80%.…”